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At the primary site, cancer cells secrete high levels of small integrin-binding ligand, N-linked glycoproteins (SIBLINGs), which favour their proliferation (osteopontin (OPN) and bone sialoprotein (BSP)) and survival (OPN, BSP and dentin matrix protein 1 (DMP1)). c | Cancer cells with enhanced adhesive and migratory capabilities can detach from the primary tumour 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 BSP, DMP1 and OPN bound to their respective receptors (αvβ3 integrins and/or CD44), which may actively promote local proteolysis through binding specific MMPs (MMP2, MMP9 and MMP3, respectively). d | As ligands for αvβ3 integrin, OPN and BSP have roles in angiogenesis. The expression of these SIBLINGs by tumour 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 tumour. e | 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 BSP, DMP1 and OPN on the cancer cell surface enables them to sequester and activate complement factor H (CFH) and protect themselves from complement-mediated lysis. f | 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 tumour progression with tumour-secreted SIBLINGs continuing to act as enhancing factors.