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Publication : The metastasis gene osteopontin: a candidate target for cancer therapy.

First Author  Weber GF Year  2001
Journal  Biochim Biophys Acta Volume  1552
Issue  2 Pages  61-85
PubMed ID  11825687 Mgi Jnum  J:74456
Mgi Id  MGI:2158510 Doi  10.1016/s0304-419x(01)00037-3
Citation  Weber GF (2001) The metastasis gene osteopontin: a candidate target for cancer therapy. Biochim Biophys Acta 1552(2):61-85
abstractText  Malignant tumors are characterized by dysregulated growth control, overcoming of replicative senescence, and metastasis formation. Current therapeutic regimens mostly exert their effects through inhibition of cell cycle progression, leaving two major components of transformation untouched. The cytokine osteopontin is essential for the dissemination of various cancers. Past research has implied several modes in which osteopontin and its main receptors on tumor cells can be suppressed. Osteopontin expression is inhibitable on the levels of gene transcription and the RNA message, and the osteopontin protein can be blocked with antibodies or synthetic peptides. The osteopontin receptor CD44 has been targeted by diverse therapeutic strategies, including cytotoxic and immunotherapeutic approaches. The receptor integrin alpha(V)beta(3) contributes not only to tumor cell dissemination, but also to angiogenesis and osteolysis in bone metastases. Small molecule inhibitors of this receptor are under study as drug candidates. Because receptors and cytokine ligands that mediate metastasis formation are sparsely expressed in the adult healthy organism and are more readily reached by pharmaceuticals than intracellular drug targets they may represent a particularly suitable focus for therapeutic intervention.
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