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Abstract
The molecular basis for the preferential metastases of certain cancers to bone is not well understood. In this issue of the JCI, Shiozawa et al. provide compelling evidence that prostate cancer cells preferentially home to the osteoblastic niche in the bone marrow, where they compete with normal HSCs for niche support. Because signals from the niche may regulate tumor quiescence and sensitivity to chemotherapy, these observations have important implications for the treatment of metastatic prostate cancer in bone.
Authors
Laura G. Schuettpelz, Daniel C. Link
Figure 1
Tumor cells compete for the HSC niche.
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(A ) HSCs reside in perivascular and endosteal niches within the bone marrow. Osteoblast lineage cells produce factors, including CXCL12, VCAM-1, and c-Kit ligand (kitL; also known as stem cell factor), that retain HSCs in the marrow and help maintain their quiescence and self-renewal capacities. (B ) PCa cells, by coopting the CXCL12/CXCR4 axis, compete with normal HSCs for residence in the niche. Signals from the niche that promote the quiescence and self-renewal of HSCs may likewise maintain tumor cells in a more stem-like state, facilitating marrow metastasis and resistance to chemotherapy.
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ISSN: 0021-9738 (print), 1558-8238 (online)