Tamoxifen restores the E-cadherin function in human breast cancer MCF-7/6 cells and suppresses their invasive phenotype

in Cancer Research (1994), 54

Extracellular matrix receptors and mouse skin carcinogenesis: altered expression linked to appearance of early markers of tumor progression.

in Cancer Research (1992), 52(10), 2966-76

Interaction of cells with the basement membrane is important for cell proliferation and differentiation. Disruption of the basement membrane is an early event during progression of benign tumors to cancer ... [more ▼]

Interaction of cells with the basement membrane is important for cell proliferation and differentiation. Disruption of the basement membrane is an early event during progression of benign tumors to cancer. Using the techniques of immunohistochemistry and immunofluorescence, we show that cell-matrix interactions via the cell surface integrin receptors alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 4, the Mr 67,000 laminin receptor (67LR) laminin-binding protein, and the secreted matrix protein laminin are strictly regulated during differentiation of mouse epidermis. While alpha 6 beta 4 and alpha 5 beta 1 are polarized to the basal surface of basal cells in contact with the basement membrane, alpha 3 beta 1 and the non-integrin 67LR are primarily detected in the cell periphery of suprabasal cells, where cell to cell contacts are found. Sequential changes in expression of matrix receptors occur following multistage carcinogenesis of mouse skin. In an analysis of benign and malignant skin tumors induced by chemical carcinogens or oncogene transduction, we found that alpha 3 beta 1 and alpha 5 beta 1 as well as the non-integrin 67LR are sequentially down-regulated in the progression from benign to malignant, while alpha 6 beta 4 is the predominant receptor expressed in the carcinomas. Tumor expression of alpha 6 beta 4 is not polarized and is dissociated from its colocalized normal partner bullous pemphigoid antigen, which remains restricted to the basement membrane. The changes in matrix receptors are linked to appearance of keratin 13 in suprabasal regions, but always in alpha 6 beta 4 negative cells. The predominance of alpha 6 beta 4 in the proliferating cells during progression is associated with decreased expression of keratin 13 in carcinomas. These results suggest that matrix interactions with its receptors are important determinants of ordered differentiation in normal skin and show characteristic alterations during carcinogenesis that parallel changes in differentiation of the tumors. [less ▲]

Invasion of Reconstituted Basement Membrane Matrix Is Not Correlated to the Malignant Metastatic Cell Phenotype

in Cancer Research (1991), 51(1), 405-14

Interactions between tumor cells and basement membranes represent a critical step in the progression of neoplasia and in the metastatic process. Reconstituted basement membrane matrix, matrigel, has been ... [more ▼]

Interactions between tumor cells and basement membranes represent a critical step in the progression of neoplasia and in the metastatic process. Reconstituted basement membrane matrix, matrigel, has been recently used with the aim of developing an in vitro assay of tumor cell invasiveness. We have extended these studies by comparing the invasiveness of a large series of normal and malignant epithelial and mesenchymal cells of human and animal origin cultured on matrigel. Normal cells (fibroblasts, glomerular mesangial cells, keratinocytes), human fibrosarcoma cells (HT1080), and reticular sarcoma cells (M5076) clearly established invasive capabilities in the matrix. However, all the other tested cell lines, malignant or virally transformed cells invasive in vivo (MCF7, T47D, SA52, SW613, MO4, A431, BeWo), as well as normal nontransformed cells (MOH22) were incapable of penetration. The morphological features of matrigel invasion by normal fibroblasts and HT1080 cells are described at the light and electron microscope levels. The extent of degradation of a radiolabeled matrigel is minimal and similar in several cell lines reported to be noninvasive or invasive in vivo. Our data suggest that matrigel does not provide a universal model to correlate the invasiveness of cells in vivo and in vitro. [less ▲]

Laminin receptor complementary DNA-deduced synthetic peptide inhibits cancer cell attachment to endothelium.

in Cancer Research (1991), 51(20), 5672-8

Stable attachment of cancer cells to the endothelium is a key step in the formation of metastasis. In this study, we have investigated the possibility that interaction between laminin and its Mr 67,000 ... [more ▼]

Stable attachment of cancer cells to the endothelium is a key step in the formation of metastasis. In this study, we have investigated the possibility that interaction between laminin and its Mr 67,000 high-affinity receptor (67 LR) could play a major role in this process. Scatchard analysis of laminin-binding studies showed that bovine aortic endothelial cells exhibit 46,000 high-affinity receptors that mediate, at least in part, the attachment of highly invasive melanoma cells. This endothelial cell-melanoma cell interaction was significantly inhibited by soluble laminin and by anti-laminin antibodies. Peptide G, an eicosapeptide derived from the complementary DNA sequence of the 67 LR precursor (IPCNNKGAHSVGLMWWMLAR) that specifically binds to laminin and presumably contains the active ligand-binding site of the receptor, specifically prevented attachment of the melanoma cells to both the bovine aortic endothelial cell monolayer and human umbilical vein endothelium. Thus, peptide G may selectively interfere with the metastatic cascade by inhibiting tumor cell attachment to endothelium via the laminin-67 LR pathway and is a potential new antimetastatic agent. [less ▲]

Immunofluorescence localization of fibronectin in chondrosarcoma cartilage matrix.

in Cancer Research (1982), 42(6), 2384-91

In this study, we have compared the extracellular matrix components and the in vitro adhesion characteristics of normal rat epiphysial chondrocytes with those from the Swarm rat chondrosarcoma, which has ... [more ▼]

In this study, we have compared the extracellular matrix components and the in vitro adhesion characteristics of normal rat epiphysial chondrocytes with those from the Swarm rat chondrosarcoma, which has many of the biochemical characteristics of normal cartilage. With the use of immunofluorescence techniques, tissue slices and chondrocytes in culture were tested for the presence of collagen types I and II, cartilage-characteristic proteoglycan, and fibronectin. Both normal and tumor matrix contained type II collagen and cartilage proteoglycan, but only the tumor matrix contained fibronectin. In culture, tumor-derived chondrocytes continued to accumulate fibronectin in their matrix, even after deposition of type II collagen and proteoglycans, while normal chondrocytes did not. When the attachment characteristics of both types of chondrocytes were compared, tumor chondrocytes required fibronectin for attachment, while normal chondrocytes used another attachment factor that had been identified previously as chondronectin. These studies suggest that, although biochemically similar to normal chondrocytes, tumor chondrocytes are no longer able to express the regulatory mechanisms for fibronectin accumulation. [less ▲]

Humoral antibody response to bovine leukemia virus infection in cattle and sheep.

in Cancer Research (1979), 39(3), 1118-1123