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Bone metastasis and the metastatic niche

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Abstract

The bone marrow has been long known to host a unique environment amenable to colonization by metastasizing tumor cells. Yet, the underlying molecular interactions within this specialized microenvironment which give rise to the high incidence of bone metastasis in breast and prostate cancer patients have long remained uncharacterized. With the recent description of the bone metastatic “niche,” considerable focus has been placed on understanding how the bone stroma contributes to each step of metastasis. Discoveries within this field have demonstrated that when cancer cells home to the niche in which hematopoietic and mesenchymal stem/progenitor cells normally reside, a bidirectional crosstalk emerges between the tumor cells and the bone metastatic stroma. This communication modulates every step of cancer cell metastasis to the bone, including the initial homing and seeding, formation of micrometastases, outgrowth of macrometastases, and the maintenance of long-term dormancy of disseminated tumor cells in the bone. In clinical practice, targeting the bone metastatic niche is evolving into a promising avenue for the prevention of bone metastatic relapse, therapeutic resistance, and other aspects of cancer progression. Here, we review the current knowledge concerning the role of the bone metastatic niche in bone metastasis.

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Acknowledgments

Research in our laboratory on bone metastasis was supported by grants from the Komen for the Cure (KG110464), Department of Defense (BC123187), the Breast Cancer Research Foundation, Brewster Foundation, and the National Institutes of Health (R01CA134519 and R01CA141062) to Y.K, an NIH K99 Award (K99CA188093) to G.R. and a pre-doctoral fellowship from the New Jersey Commission on Cancer Research to M.E.

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  1. Department of Molecular Biology, Princeton University, LTL255, Washington Road, Princeton, NJ, 08544, USA

    Guangwen Ren, Mark Esposito & Yibin Kang

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  1. Guangwen Ren
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  2. Mark Esposito
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Correspondence to Yibin Kang.

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Ren, G., Esposito, M. & Kang, Y. Bone metastasis and the metastatic niche. J Mol Med 93, 1203–1212 (2015). https://doi.org/10.1007/s00109-015-1329-4

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