References of "Castronovo, Vincenzo"
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See detailExpression of Bone Sialoprotein in Primary Human Breast Cancer Is Associated with Poor Survival
Bellahcene, Akeila ULg; Menard, S.; Bufalino, R. et al

in International Journal of Cancer = Journal International du Cancer (1996), 69(4), 350-3

We have recently demonstrated that bone sialoprotein (BSP), a bone-matrix protein involved in hydroxyapatite crystal formation, is ectopically expressed in human breast cancers. We explored a possible ... [more ▼]

We have recently demonstrated that bone sialoprotein (BSP), a bone-matrix protein involved in hydroxyapatite crystal formation, is ectopically expressed in human breast cancers. We explored a possible association between expression of BSP in primary breast cancer and patients' survival. We analyzed BSP expression in 454 breast-cancer patients by immunohistochemistry on archival paraffin-embedded material using an anti-BSP polyclonal antibody. BSP expression was correlated to survival, tumor size, axillary lymph-node status and first site of distant metastasis. Of the breast cancers analyzed, 89% expressed detectable amounts of BSP. We found a statistical association between expression of BSP and poor prognosis as indicated by survival curves analyzed using the log rank and the Gehan methods. BSP expression was significantly higher in breast-cancer patients with axillary lymph-node involvement. Interestingly, survival of patients with positive lymph nodes but BSP-negative tumors was significantly higher than that of patients with no lymph-node involvement but BSP-positive cancers. The frequency of bone metastases was higher in the group of patients with BSP-positive tumors (22%) than in the group with BSP-negative cancers (7%). There was a significant increase in the incidence of lung metastases in patients whose tumors were negative for BSP. Our data show that bone sialoprotein expression in breast cancer is associated with poor prognosis. BSP detection also appears to be a valuable marker with which to identify, among the lymph-node-negative patients, those who have high risk of disease progression. [less ▲]

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See detailIsolation from a multigene family of the active human gene of the metastasis-associated multifunctional protein 37LRP/p40 at chromosome 3p21.3.
Jackers, Pascale ULg; Minoletti, Fabiola; Belotti, Dorina et al

in Oncogene (1996), 13(3), 495-503

The 37 kD precursor of the 67 kD laminin receptor (37LRP) is a polypeptide whose expression is consistently upregulated in aggressive carcinoma. Interestingly, the 37LRP appears to be a multifunctional ... [more ▼]

The 37 kD precursor of the 67 kD laminin receptor (37LRP) is a polypeptide whose expression is consistently upregulated in aggressive carcinoma. Interestingly, the 37LRP appears to be a multifunctional protein involved in the translational machinery and has also been identified as p40 ribosome-associated protein. Although highly conserved cDNAs corresponding to this polypeptide have been isolated from several species including vertebrates, invertebrates, plants and prokaryotes, characterization of any of the corresponding active genes has never been reported. In this study, we have cloned an intron-containing fragment which permitted us to isolate the active 37LRP/p40 human gene. This gene contains seven exons and six introns. Ribonuclease protection experiments suggest multiple transcription start sites. The promoter area does not bear a TATA box but contains four Sp1 sites. The first intron is also GC rich containing five Sp1 sites. Intron 4 contains the full sequence of the small nuclear RNA E2 and two Alu sequences are found in intron 3. Fluorescent in situ hybridization localized the 37LRP/p40 active gene on chromosome 3 in the locus 3p21.3 which, interestingly, is a hot spot for genetic alterations in several cancers and particularly in small cell lung carcinoma. [less ▲]

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See detailExpression of the 67 Kd Laminin Receptor in Human Ovarian Carcinomas as Defined by a Monoclonal Antibody, Mluc5
van den Brule, F. A.; Castronovo, Vincenzo ULg; Menard, S. et al

in European Journal of Cancer (1996), 32A(9), 1598-602

Previous immunohistochemical data from our laboratory have demonstrated that expression of the 67 kD laminin receptor (67LR), a cancer-associated, high-affinity laminin-binding protein, is upregulated in ... [more ▼]

Previous immunohistochemical data from our laboratory have demonstrated that expression of the 67 kD laminin receptor (67LR), a cancer-associated, high-affinity laminin-binding protein, is upregulated in ovarian carcinoma cells compared with normal serosal cells, and that this increased expression in cancer cells could be related to patient outcome. The aim of this study was to validate MLuC5, a monoclonal antibody that recognises the 67LR, as a tool to perform future immunohistochemical studies on larger populations of ovarian carcinoma patients. Expression of the 67LR was determined in 51 primary human ovarian carcinoma samples using immunohistochemistry and MLuC5. The 67LR was detected in ovarian carcinoma cell clusters of variable extent. Analysis of the data determined that 67LR expression was significantly increased in the samples from patients with disease progression, compared with those with no evidence of disease after completion of primary therapy, and in pooled grade 2 and 3 tumours compared to borderline and grade 1 tumours (P < 0.05, chi-squared test). No other significant correlation between 67LR expression and other clinicopathological parameters could be established. These data suggest that the 67LR is correlated to ovarian tumour progression. Detection of the 67LR using this monoclonal antibody could constitute an interesting parameter in prognosis determination of ovarian cancer. [less ▲]

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See detailDetection of Bone Sialoprotein in Human Breast Cancer Tissue and Cell Lines at Both Protein and Messenger Ribonucleic Acid Levels
Bellahcene, Akeila ULg; Antoine, Nadine ULg; Clausse, N. et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (1996), 75(2), 203-10

The recent demonstration that bone sialoprotein (BSP) can be detected in human breast cancer tissue by immunoperoxidase suggests that this phosphoprotein is ectopically expressed by malignant mammary ... [more ▼]

The recent demonstration that bone sialoprotein (BSP) can be detected in human breast cancer tissue by immunoperoxidase suggests that this phosphoprotein is ectopically expressed by malignant mammary epithelial cells. Its detection in human breast cancer cells raises questions about its potential role(s) during breast cancer progression. Because BSP is secreted and is present in the serum, the positivity of breast cancer cells for BSP could have been the result of an uptake of the circulating phosphoprotein by the cells rather than of an intrinsic expression. We examined the expression of BSP at both the protein and mRNA levels in nine human breast cancer samples as well as in three human breast cancer cell lines (MCF-7, T47-D, and MDA-MB-231) using immunohistochemistry, flow cytometric analysis, immunoblot, and reverse-transcriptase PCR. BSP was detected at both protein and mRNA levels in human breast cancer tissue and in the three human breast cancer cell lines. Using a specific polyclonal anti-BSP antibody, we showed by both fluorescence-activated cell sorter analysis and immunohistochemistry experiments that all of the human breast cancer cell lines studied express BSP. This was localized at the cell surface and in the cytosol of the estrogen receptor-positive MCF-7 and T47-D cell lines, whereas it was detected only in the cytosol of the estrogen receptor-negative MDA-MB-231 cells. Using the same polyclonal anti-BSP antibody, we were able to identify an approximately 97-kd band on total protein extracts from the three cell lines by immunoblotting. Reverse-transcriptase PCR reactions using specific oligonucleotides performed on total RNA of nine human breast cancer biopsy samples and the three cell lines demonstrated the presence of BSP mRNA in all of the samples examined. This study is the first demonstration that human malignant breast epithelial cell lines express BSP at the protein and mRNA levels. Our study identified MCF-7, T47-D, and MDA-MB-231 cells as useful models for the examination of the molecular mechanisms involved in the ectopic expression of BSP in breast malignant lesions. [less ▲]

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See detailDetection of Hoxa1 Expression in Human Breast Cancer
Chariot, Alain ULg; Castronovo, Vincenzo ULg

in Biochemical and Biophysical Research Communications (1996), 222(2), 292-7

Homeodomain-containing proteins are transcription factors that regulate the coordinated expression of multiple genes involved in development, differentiation and malignant transformation. To better ... [more ▼]

Homeodomain-containing proteins are transcription factors that regulate the coordinated expression of multiple genes involved in development, differentiation and malignant transformation. To better understand the role played by these proteins in breast cancer cells, we demonstrate, using semi-quantitative RT-PCR experiments, that progestin induces HOXA1 mRNAs in MCF7 cells. This is the first evidence of regulation of a HOX gene by steroids. Moreover, we detected HOXA1 expression in a variety of human breast cancer lesions, suggesting that HOXA1 may be required for the establishment of breast cancer cells phenotype. We propose that HOXA1 gene could be one of the orchestrators that regulate breast epithelial cell differentiation and that alteration of HOXA1 expression could play a role in breast cancer progression. [less ▲]

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See detailBone Sialoprotein Expression in Primary Human Breast Cancer Is Associated with Bone Metastases Development
Bellahcene, Akeila ULg; Kroll, M.; Liebens, F. et al

in Journal of Bone and Mineral Research (1996), 11(5), 665-70

Breast cancer metastasizes to bone more frequently than to any other organ, and over 80% of advanced breast cancer patients develop bone metastases. Our recent demonstration that human breast cancer cells ... [more ▼]

Breast cancer metastasizes to bone more frequently than to any other organ, and over 80% of advanced breast cancer patients develop bone metastases. Our recent demonstration that human breast cancer cells express bone sialoprotein (BSP), a bone matrix protein, provides a possible clue for the selective affinity of breast cancer cells for bone. We tested the hypothesis that detection of BSP in primary human breast cancer could be a potential indicator of the ability of breast cancer cells to metastasize to bone. BSP expression was evaluated in the primary breast cancers of 39 patients using immunoperoxidase and two specific anti-BSP antibodies. None of these patients presented clinically or scintigraphically detectable bone metastases at the time of surgery. In the course of their disease, 22 patients developed clinically diagnosed bone metastases. Expression of BSP in breast cancer cells from patients who developed bone metastases was significantly higher (p = 0.008, according to the Mann-Whitney test) than in patients with no bone involvement. No association was found between BSP expression in the primary breast lesions and axillary lymph node metastases. BSP expression was significantly increased in infiltrating ductal carcinoma compared with infiltrating lobular carcinoma (p = 0.0023). No correlation was found between immunoreactivity to BSP antibodies and estrogen receptor (ER) status, progesterone receptor (PR) status, or age. Our data suggest that BSP could help to identity which women will develop bone metastases and provide new bases for the understanding of the molecular mechanism(s) responsible for breast cancer cells osteotropism. [less ▲]

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See detailDecreased expression of galectin-3 is associated with progression of human breast cancer.
Castronovo, Vincenzo ULg; van den Brule, Frédéric; Jackers, Pascale ULg et al

in Journal of Pathology (The) (1996), 179(1), 43-48

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of ... [more ▼]

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of galectin-3 during the interactions between cells and laminin is not yet known, it has recently been observed that its expression is down-regulated at both the protein and the mRNA level in colon cancer tissues in correlation with progression of the disease. This study investigated the possibility that breast cancer cells might also exhibit decreased galectin-3 expression in association with their aggressiveness. The expression of galectin-3 was examined by immunoperoxidase staining, using a polyclonal antibody raised against recombinant galectin-3, in a collection of 98 human breast lesions including 12 fibroadenomas, 15 fibrocystic disease lesions, 22 in situ carcinomas, and 49 infiltrating ductal carcinomas, 19 of which had positive axillary lymph nodes. Normal breast tissue adjacent to the lesions was present in 59 biopsies. Normal breast tissue expressed high levels (3+) of galectin-3. High expression (2+ to 3+) was also found in most benign lesions examined. The expression of galectin-3 was significantly decreased in in situ carcinoma and this down-regulation was more pronounced in invasive ductal carcinoma, particularly when associated with infiltration of axillary lymph nodes. These data constitute the first observation that galectin-3 is down-regulated in breast cancer and suggest the decreased expression of this galactoside-binding lectin is associated with the acquisition of the invasive and metastatic phenotype. [less ▲]

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See detailOverexpression of the 67-kDa laminin receptor correlates with tumor progression in human prostate cancer
Waltregny, David ULg; de Leval, Laurence ULg; Ménard, Sylvie et al

in Clinical & Experimental Metastasis (1996, March), 14(Suppl. 1), 1996

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See detailSeventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events
Jackers, Pascale ULg; Clausse, Nathalie; Fernandez, Maria-Teresa et al

in Biochimica et Biophysica Acta (1996), 1305(1-2), 98-104

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40 ... [more ▼]

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40). Interestingly, increased expression of this polypeptide (37LRP/p40) is consistently observed in invasive and metastatic cancer cells and is associated with poor prognosis. Southern-blot analysis of human genomic DNA predicted multiple copies of the 37LRP/p40 gene. In this study, we report that the number of copies of this sequence in the human genome is 26 +/- 2. We have sequenced and analyzed 19 genomic clones corresponding to the 37LRP/p40 gene and found that they were all processed pseudogenes. They all lack intronic sequences and show multiple genetic alterations leading in some cases to the appearance of stop codons. Moreover, they all bear characteristic features of retroposons as the presence of a poly(A)-tail at their 3' end and short direct repeated flanking DNA sequences. None of the pseudogenes analyzed present cis-elements in their 5' flanking region such as TATA or GC boxes. Our date reveal that over 50% of the 37LRP/p40 gene copies are pseudogenes most probably generated by retropositional events. The finding of multiple pseudogenes for the 37LRP/p40 suggests that the accumulation of several copies of this gene might have given a survival advantage to the cell in the course of evolution. [less ▲]

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See detailIn Vitro and in Vivo Stimulation of the Murine Immune System by Agm-1470, a Potent Angiogenesis Inhibitor
Antoine, Nadine ULg; Daukandt, M.; Heinen, Ernst ULg et al

in American Journal of Pathology (1996), 148(2), 393-8

AGM-1470, a potent angiogenesis inhibitor, is already engaged in phase I clinical trials because of its effectiveness to restrain tumor growth and its lack of major side effects. Recently, we showed that ... [more ▼]

AGM-1470, a potent angiogenesis inhibitor, is already engaged in phase I clinical trials because of its effectiveness to restrain tumor growth and its lack of major side effects. Recently, we showed that AGM-1470 stimulates in vitro human B lymphocyte proliferation through T lymphocytes. These data prompted us to explore the in vivo effects of AGM-1470 on the immune system in a mouse model. In this study, we showed that AGM-1470, in synergy with phytohemagglutinin, stimulates the proliferation of murine lymphocytes isolated from lymph nodes. This effect was similar to the one observed with human lymphocytes. When injected subcutaneously or intraperitoneally into mice at pharmacological doses, AGM-1470 induced a significant increase of axillary and mesenteric lymph nodes, respectively. Histological and morphological analyses showed that this phenomenon is mostly due to a hyperplasia of the germinal centers. On average, the area of the germinal center of lymph nodes from AGM-1470-treated mice were three times larger than in lymph nodes from control mice. Interestingly, no effect was observed when AGM-1470 was injected subcutaneously into T-deficient nude mice. Our data demonstrate that AGM-1470 stimulates B cell proliferation in vivo as suggested by the in vitro experiments. This effect should be taken into account in the follow-up of patients treated with this molecule and calls for additional studies to determine the biological consequences of such a stimulation on the host immune system. [less ▲]

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See detailShedding of the 67-kD laminin receptor by human cancer cells.
Karpatova, M.; Tagliabue, E.; Castronovo, Vincenzo ULg et al

in Journal of Cellular Biochemistry (1996), 60(2), 226-34

The 67-kD laminin receptor (67LR) is a cell membrane-associated molecule exhibiting high affinity for the basement membrane glycoprotein, laminin. While export of the 67LR toward the extracellular matrix ... [more ▼]

The 67-kD laminin receptor (67LR) is a cell membrane-associated molecule exhibiting high affinity for the basement membrane glycoprotein, laminin. While export of the 67LR toward the extracellular matrix has been recently suggested by electron microscopy studies, there is to date no evidence of shedding of the 67LR from cells. Using two monoclonal antibodies directed against the 67LR, we developed a double-determinant radioimmunoassay that demonstrates that the 67LR is released from cancer cells into the culture medium. The shed molecule exhibited the same apparent molecular weight as that of the membrane-associated 67LR, suggesting that no proteolytic cleavage is involved in the process. Furthermore, we demonstrate that the 67LR is not anchored to the membrane through a glycolsyl-phosphatidylinositol bridge. However, the observation that lactose increased the release of 67LR suggests that a lectin-type interaction is involved in the cell membrane association of this laminin binding protein and the cell surface. Interestingly, the released 67LR recovered after HPLC gel filtration was found free as well as associated to high molecular weight complexes. The free 67LR retained its ability to bind to the cell surface. Our study is the first demonstration that the 67LR is effectively shed by cancer cells. The released free 67LR could play an important role in modulating interactions between cancer cells and laminin during tumor invasion and metastasis. [less ▲]

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See detailExpression of the Mr 67,000 laminin receptor is an adverse prognostic indicator in human thyroid cancer: an immunohistochemical study.
Basolo, F.; Pollina, L.; Pacini, F. et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (1996), 2(10), 1777-80

Increased expression of the Mr 67,000 laminin receptor (LR) is a consistent event which appears as cancer cells acquire an invasive and metastatic phenotype. The Mr 67,000 LR is one of the many laminin ... [more ▼]

Increased expression of the Mr 67,000 laminin receptor (LR) is a consistent event which appears as cancer cells acquire an invasive and metastatic phenotype. The Mr 67,000 LR is one of the many laminin-binding proteins able to interact with the major glycoprotein of basement membranes, laminin. The recent development of a specific monoclonal antibody directed against the Mr 67,000 LR MLuC5 has allowed us to study large retrospective groups of human cancers with the aim of correlating the Mr 67,000 LR expression to the clinical, pathological, and survival data of the patients. A significant correlation has already been established between the increased expression of Mr 67,000 LR and survival of patients with breast, colon, ovary, lung, and endometrial cancers. In this study, we investigated the possibility that the detection of Mr 67,000 LR in thyroid human cancers could also be of prognostic value. We analyzed the expression of Mr 67,000 LR with immunohistochemistry using MLuC5 antibodies in paraffin sections of 40 benign and 170 malignant thyroid human tumors. We found that Mr 67,000 LR was not usually detectable in normal thyroid tissues adjacent to the lesion. Only 3 of the 40 thyroid adenomas examined (7.5%) presented cells positive for Mr 67,000 LR. For the malignant thyroid tumors examined, we found that 22.3% of papillary thyroid carcinomas, 38% of follicular thyroid carcinomas, 40% of poorly differentiated carcinomas, 25% of medullary carcinomas, and 58.3% of anaplastic carcinomas expressed a high level of Mr 67,000 LR. Although no correlation between the Mr 67,000 LR expression and survival was found in patients with follicular thyroid carcinomas, papillary thyroid carcinomas, anaplastic carcinomas, and medullary carcinomas, there was a significant correlation in primary thyroid cancers. Our data represent the first extensive study of the Mr 67,000 LR expression in human thyroid cancers and strongly suggest that its detection could be of prognostic value in the investigation of primary thyroid cancers. [less ▲]

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See detailOverexpression of the 67-kD laminin receptor correlates with tumour progression in human colorectal carcinoma.
Sanjuan, X.; Fernandez, P. L.; Miquel, R. et al

in Journal of Pathology (The) (1996), 179(4), 376-80

The high affinity 67-kD laminin receptor (67LR) is a cell surface protein whose expression is increased in a number of human carcinoma models. To date, 67LR expression in colorectal carcinomas has been ... [more ▼]

The high affinity 67-kD laminin receptor (67LR) is a cell surface protein whose expression is increased in a number of human carcinoma models. To date, 67LR expression in colorectal carcinomas has been examined in a small number of cases. 67LR expression has been immunohistochemically analysed in a large series of human colorectal neoplasms, using the MLuC5 monoclonal antibody. The study included 59 samples of non-neoplastic mucosa, 45 polyps (11 hyperplastic, 34 adenomas), 196 carcinomas, and lymph node metastases of 87 carcinomas. Epithelial cells of normal mucosa and hyperplastic polyps were negative or showed weak positivity in the paranuclear and apical areas of the cytoplasm. In adenomas and carcinomas, the staining was stronger, with a membranous or cytoplasmic pattern. The expression of 67LR correlated significantly with the progression from normal mucosa (22 per cent) to adenoma (44 per cent), carcinoma (61 per cent), and lymph node metastasis (75 per cent) (P < 0.0001). Expression of the laminin receptor showed a tendency to be more frequently positive in advanced stage (III+IV; 67 (III+IV; 67 per cent) when compared with early stage (I+II) carcinomas (54 per cent). The difference, however, was not statistically significant (P = 0.058). In addition, 14 out of 28 (50 per cent) primary carcinomas without 67LR expression became positive in lymph node metastases, while most (86 per cent) of the MLuC5-positive primary carcinomas were also immunoreactive in metastases. In conclusion, these results indicate that 67LR is up-regulated in the progression of human colorectal carcinomas and may play a role in the local and metastatic progression of these tumours. [less ▲]

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See detailPeptide G, containing the binding site of the 67-kDa laminin receptor, increases and stabilizes laminin binding to cancer cells.
Magnifico, A.; Tagliabue, E.; Buto, S. et al

in Journal of Biological Chemistry (1996), 271(49), 31179-84

We investigated the effect of peptide G, a synthetic peptide derived from the sequence of the 37-kDa laminin receptor precursor, on the interaction of laminin in two tumor cell lines one of which produces ... [more ▼]

We investigated the effect of peptide G, a synthetic peptide derived from the sequence of the 37-kDa laminin receptor precursor, on the interaction of laminin in two tumor cell lines one of which produces laminin and one of which does not. Addition of peptide G to the culture medium induced a significant increase in the amount of endogenous laminin detectable on the cell membrane of both cell lines. Moreover, pretreatment of exogenous laminin with peptide G dramatically increased laminin binding on both cell lines. Kinetics analysis of membrane-bound labeled laminin revealed a 3-fold decrease in the kd of peptide G-treated laminin compared with untreated or unrelated or scrambled peptide-treated laminin. Moreover, the affinity constant of peptide G-treated laminin increased 2-fold, with a doubling of the number of laminin binding sites, as determined by Scatchard analysis. Expression of the VLA6 integrin receptor on the cell membrane increased after incubation with peptide G-treated laminin. However, the lower binding inhibition of peptide G-treated laminin after anti-VLA6 antibody or cation chelation treatment indicates that membrane molecules in addition to integrin receptors are involved in the recognition of peptide G-modified laminin. These "new" laminin-binding proteins also mediated cell adhesion to laminin, the first step in tumor invasion. Together, the data suggest that peptide G increases and stabilizes laminin binding on tumor cells, involving surface receptors that normally do not take part in this interaction. This might explain the abundant clinical and experimental data suggesting a key role for the 67-kDa laminin receptor in the interaction between cancer cells and the basement membrane glycoprotein laminin during tumor invasion and metastasis. [less ▲]

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See detailA Possible Role for the Alpha 1-->3 Galactosyl Epitope and the Natural Anti-Gal Antibody in Oncogenesis
Gollogly, L.; Castronovo, Vincenzo ULg

in Neoplasma (1996), 43(5), 285-9

Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 ... [more ▼]

Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed. [less ▲]

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See detailCloning and expression of a new HOXC6 transcript encoding a repressing protein
Chariot, Alain ULg; Castronovo, Vincenzo ULg; Le, P. et al

in Biochemical Journal (1996), 319

Homeodomain-containing proteins are transcription factors that regulate the co-ordinated expression of multiple genes involved in development, differentiation and malignant transformation. In an attempt ... [more ▼]

Homeodomain-containing proteins are transcription factors that regulate the co-ordinated expression of multiple genes involved in development, differentiation and malignant transformation. In an attempt to characterize expressed homeobox (HOX) genes in breast cancer cells, we cloned two distinct HOXC6 transcripts from an MCF7 cDNA library, Interestingly, one of them represents a new HOXC6 mRNA encoding a homeodomain-containing protein harbouring a unique N-terminal sequence. Moreover we demonstrate that this HOXC6 transcript is less abundant in human breast cancer cells than in non-tumorigenic cell lines, is detected in breast carcinomas and adjacent tissues and is expressed in a variety of human tumours. In addition, transient co-transfection experiments illustrated that both HOXC6 transcripts encode gene products that repress transcription from a HOX binding sequence in MDA-MB231 cells and co-operate with other HOX gene products such as HOXB7 on their target genes. Taken together, our results suggest that HOXC6 proteins might contribute to the breast cell phenotype through co-operative interactions with other HOX-derived proteins and repression of their target genes. [less ▲]

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See detailRecent advances in prostate cancer metastasis
Waltregny, David ULg; Castronovo, Vincenzo ULg

in Tumori (1996), 82(3, May-Jun), 193-204

Prostate cancer in men has now surpassed lung cancer as the most frequent non-cutaneous cancer. From a biological perspective, prostate carcinoma is unique among human malignancies in the wide discrepancy ... [more ▼]

Prostate cancer in men has now surpassed lung cancer as the most frequent non-cutaneous cancer. From a biological perspective, prostate carcinoma is unique among human malignancies in the wide discrepancy that exists between the prevalence of 'latent' cancer, recognizable only histologically, and that of the clinical disease. Histologically detected localized prostate cancers are heterogeneous, with only a small subset having undergone all of the malignant changes required to produce clinically aggressive tumors. Most of these 'latent' carcinoma never become fully malignant and do not threaten the life or well-being of the host. At present, it is not possible to predict which localized cancers will progress to clinically overt disease. Likewise, many patients have underevaluated and unpredictable extent of their prostate carcinoma, thus resulting in inadequate therapeutic strategies. It is clear that we need to identify molecular and/or cellular markers that are able to define the invasive and metastatic potential of prostate cancer on an individual patient basis. Acquisition of metastatic ability is a definitive criterion by which substage localized prostate cancers. Under the light of recent studies designed to identify some of the features associated with the metastatic phenotype of prostate cancer, the authors review recent advances aimed at gaining insight into those factors that may be involved in prostate cancer metastasis. [less ▲]

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See detailThe human 37kDa laminin receptor precursor/p40 ribosomal associated protein multigene family : structure of the active gene and chromosomal location at 3p21.3
Jackers, Pascale ULg; Minoletti, Fabiola; Belotti, Dorina et al

in Cell Biology International (1996), 20

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See detailTamoxifen and the E-Cadherin/Catenin complex.
Bracke, M.; Van Roy, Frans; Castronovo, Vincenzo ULg et al

in In The Enigma of Tamoxifen. (1996)

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