title: Osteopontin as a therapeutic target for cancer.
abstract: BACKGROUND
  Cancer is a complex pathological disorder, established as a result of accumulation of genetic and epigenetic changes, which lead to adverse alterations in the cellular phenotype. Tumor progression involves intricate signaling mediated through crosstalk between various growth factors, cytokines and chemokines. Osteopontin (OPN), a chemokine-like protein, is involved in promotion of neoplastic cancer into higher grade malignancies by regulating various facets of tumor progression such as cell proliferation, angiogenesis and metastasis.
  
  
  METHODS
  Tumors as well as stroma-derived OPN play key roles in various signaling pathways involved in tumor growth, angiogenesis and metastasis. OPN derived from tumor-activated macrophages modulates the tumor microenvironment and thereby regulate melanoma growth and angiogenesis. OPN also regulates hypoxia-inducible factor-1α-dependent VEGF expression leading to breast tumor growth and angiogenesis in response to hypoxia. Thus, a clear understanding of the molecular mechanism underlying OPN-mediated regulation will shed light on exciting avenues for further investigation of targeted therapies. Silencing of OPN using RNAi technology, blocking OPN activity using specific antibodies and small-molecule inhibitors might provide novel strategies, which would aid in developing effective therapeutics for the treatment of various types of cancer.
  
  
  CONCLUSIONS
  This review focuses on new possibilities to exploit OPN as a tumor and stroma-derived therapeutic target to combat cancer.
authors.affiliation: Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS) , Pune 411007 , India kundu@nccs.res.in.
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mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000628:therapy*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D053495:Osteopontin
keywords: RNAi technology; angiogenesis; biomarker; hypoxia; osteopontin; stroma; targeted therapy