Interactions Between Disseminated Tumor Cells and Bone Marrow Stromal Cells Regulate Tumor Dormancy
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Purpose of Review
To succinctly summarize recent findings concerning dormancy regulating interactions between bone marrow stromal cells and disseminated tumor cells.
Recent studies have highlighted roles of the bone marrow microenviroment, including osteoblasts, mesenchymal stem cells (MSCs), and endothelial cells, in inducing or maintaining cancer cell dormancy. Key pathways of interest include: osteoblast-induced transforming growth factor (TGF)-β2 signaling, transfer of MSC-derived exosomes containing dormancy inducing microRNA, cancer cell cannibalism of MSCs, and endothelial cell secretion of thrombospondin 1 (TSP1).
The bone marrow is a common site of metastatic disease recurrence following a period of cancer cell dormancy. Understanding why disseminated tumor cells enter into dormancy and later resume cell proliferation and growth is vital to developing effective therapeutics against these cells. The bone marrow stroma and the various pathways through which it participates in crosstalk with cancer cells are essential to furthering understanding of how dormancy is regulated.
KeywordsCancer cell dormancy Bone marrow microenviroment Bone marrow stromal cells Osteoblasts Mesenchymal stem cells Endothelial cells
This work is directly supported by Department of Defense (W81XWH-14-1-0403, Y. Shiozawa; W81XWH-17-1-0541, Y. Shiozawa), the Wake Forest Baptist Comprehensive Cancer Center Internal Pilot Funding (Y. Shiozawa), and the Wake Forest School of Medicine Internal Pilot Funding (Y. Shiozawa). Y Shiozawa is supported as the Translational Research Academy which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001420. This work is also supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.
Compliance with Ethical Standards
Conflict of Interest
D. Brooke Widner, Sun H. Park, Matthew R. Eber, and Yusuke Shiozawa declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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