Molecular SIBLINGs in Health and Disease
Osteopontin in cancer.
Altered OPN levels have been associated with a number of cancers including breast cancer (1-9), gastrointestinal stromal tumors(1011), leukemia (12-15), lung cancer (16-21), pancreatic (22-25) and renal cell carcinoma (26-28). OPN has biological plausibility to be playing an active role in key stages of tumor progression.

Role of OPN at different steps of the metastatic cascade

At the primary site, cancer cells secrete high levels of OPN, which favor their (A) survival and (B) proliferation. Cancer cells with enhanced adhesive and migratory capabilities can detach from the primary tumor mass and degrade the basement membrane to invade the stroma. The associated proteolysis of the extracellular matrix (ECM) is mediated through matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA). OPN enhances uPA activation, cell motility and invasion into the surrounding tissue. The insert shows OPN bound to αvβ3 integrin and/or CD44, which may actively promote local proteolysis through binding MMP3 (C). The expression of OPN by tumor cells promotes the migration and adhesion of activated endothelial cells, which are crucial during angiogenesis. OPN acts as a chemotactic and adhesion molecule for macrophages and promotes their infiltration of the tumor (D). The transport of cancer cells in the circulation is one of the limiting steps for metastasis to distant organs because they are confronted by the host immune system. The insert shows that, in this context, the expression and the presentation of OPN on the cancer cell surface enables them to sequester and activate complement factor H  and protect themselves from complement-mediated lysis (E).  At distant site(s), cancer cell extravasation is followed by the formation of a secondary colony. Proliferative, survival and angiogenenic signals by newly formed metastatic colonies occur mainly through mechanisms similar to those that are used during the early steps of tumor progression with tumor-secreted OPN continuing to act as a progression promoter.


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