PROGRESSION OF BREAST CANCER METASTATIC DISEASE AND SUBSEQUENT OSTEOLYTIC BONE DEGRADATION MEDIATED BY ONCOSTATIN M By

Metastatic events to the bone occur frequently in numerous cancer types such as breast,prostate, lung and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma.Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) isfrequently upregulated and is implicated in the ability of cancer cells to metastasize tobone. IL-6 is able to activate various cell signaling cascades that include the signaltransducers and activator of transcription (STAT) pathway, the phosphatidylinositol-3kinase (PI3K) pathway, and the mitogen-activated protein kinase (MAPK) pathway.Activation of these pathways may explain the ability of IL-6 to mediate various aspectsof normal and pathogenic bone remodeling, inflammation, cell survival, proliferation,and pro-tumorigenic effects. This review article will discuss the role of IL-6: i) in bonemetabolism, ii) in cancer metastasis to bone, iii) in cancer prognosis, and iv) aspotential therapies for metastatic bone cancer.