[en] The 16-kDa N-terminal fragment of human prolactin (16K hPRL) is a potent angiostatic factor that inhibits tumor growth in mouse models. Using microarray experiments, we have dissected how the endothelial-cell genome responds to 16K hPRL treatment. We found 216 genes that show regulation by 16K hPRL, of which a large proportion turned out to be associated with the process of immunity. 16K hPRL induces expression of various chemokines and endothelial adhesion molecules. These expressions, under the control of nuclear factor-kappaB, result in an enhanced leukocyte-endothelial cell interaction. Furthermore, analysis of B16-F10 tumor tissues reveals a higher expression of adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, or E-selectin) in endothelial cells and a significantly higher number of infiltrated leukocytes within the tumor treated with 16K hPRL compared with the untreated ones. In conclusion, this study describes a new antitumor mechanism of 16K hPRL. Because cellular immunity against tumor cells is a crucial step in therapy, the discovery that treatment with 16K hPRL overcomes tumor-induced anergy may become important for therapeutic perspectives.
Research center :
Giga-Cancer - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Tabruyn, Sébastien ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Sabatel, Céline ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Nguyen, Ngoc-Quynh-Nhu ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Verhaeghe
Castermans, Karolien ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Malvaux, Ludovic ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Griffioen, A. W.
Martial, Joseph ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Struman, Ingrid ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Language :
English
Title :
The angiostatic 16K human prolactin overcomes endothelial cell anergy and promotes leukocyte infiltration via nuclear factor-kappaB activation
Publication date :
2007
Journal title :
Molecular Endocrinology
ISSN :
0888-8809
eISSN :
1944-9917
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
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