Mechanisms of bone metastases

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

A striking feature of many neoplasms is their tendency to metastasize to bone. For metastases to occur, the malignant cells must first escape from the primary tumor, penetrate and circulate through the bloodstream and subsequently arrest in the target tissues. The production of chemotactic factors of bone cells, the distribution of venous plexuses, the presence of "leaky" marrow sinusoids, and or the production of growth factors that provide a selective advantage in bone (seed in soil hypothesis) all are likely to play important role sin the metastatic pattern. Yet the molecular basis for how these tumors 'home' to bone remains to be determined. hematopoietic stem cells also 'home' to bone; both during development and in therapeutic marrow transplantation. In this context, the recently identified CXC chemokine stromal-derived factor 1-SDF-1) and its receptor, CXCR4, have been shown to play an important role. We hypothesize that metastatic carcinomas also utilize the SDF-1/CXCR4 pathway to localize on the marrow. In this proposal this hypothesis will be tested by using prostate cancer as a model of bone metastasis.