The metastasis gene osteopontin: a candidate target for cancer therapy.
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.
Weber
G F
GF
Department of Radiation Oncology, New England Medical Center and Tufts University Medical School, 750 Washington Street, NEMC #824, Boston, MA 02111, USA. gweber@lifespan.org
D000818:Animals; D001665:Binding Sites; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000378:metabolism; D007167:Immunotherapy; D019012:Integrin beta1 / Q000187:drug effects; D009362:Neoplasm Metastasis / Q000235:genetics*; D009369:Neoplasms / Q000628:therapy*; D053495:Osteopontin; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000276:immunology; D012795:Sialoglycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism
D016207:Cytokines; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin