The metastasis of tumor cells to distant organs is the primary cause of cancer-related mortality in most cancers. The interaction of tumor cells with local stroma at the metastatic site plays a critical role in metastatic dissemination and the establishment of metastases. These tumor-stromal interactions regulate several important steps including degradation of extracellular matrix, release of sequestered growth factors, and expression of chemokines, cytokines, and receptors on tumor cells and the interacting stromal cells. Breast, prostate, and lung cancers preferentially metastasize to bone. Tumor cell interactions with the bone microenvironment initiate a series of complex cellular interactions that promotes establishment of osteoclastic and/or osteoblastic metastasis. Understanding the interactions between tumor cells and the stroma is important to identify molecular targets to develop novel therapies aimed at reducing metastasis formation. In this article, we review the important mechanisms of tumor-stromal interaction in the development of bone metastasis.
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