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Dormancy and Recurrence of Cancer Stem Cells in Bone: Role of Bone Morphogenetic Proteins

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Tumor Dormancy, Quiescence, and Senescence, Volume 2

Part of the book series: Tumor Dormancy and Cellular Quiescence and Senescence ((DOQU,volume 2))

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Abstract

Metastatic disease is the leading cause of death in cancer patients. Despite significant advancement in understanding the pathological process at cellular and molecular level, there is no effective cure to this devastating disease till date. Dissemination of cancer cell into the blood is considered to occur even at an early stage in cancer progression that eventually leads to formation of secondary tumor or metastasis after remaining dormant for a long or short period of time. This variation in time period can be attributed to the properties of both disseminated tumor cells and the new homing microenvironment at the metastatic sites. Increasing line of evidences indicate that the disseminated cells possess cancer stem cell like properties that render them with the ability to disseminate from primary tumor and remain dormant in the new microenvironment at the distant organs. However, it is not clear about how and when these cancer stem-like cells (CSCs) are able to switch into proliferative state to manifest as recurrent disease. CSCs must adopt different genetic and epigenetic changes to potentiate themselves with proliferative phenotype leading to recurred tumor. On the other hand, immediate microenvironment of CSCs exerts restrictive barrier for growth of these cells or even induce cell death. To evade from the inhibitory signaling from the microenvironment, these disseminated CSCs switch to dormant phenotype. It has been recently found that bone morphogenetic proteins (BMPs) released by microenvironmental cells plays a critical role in inducing dormancy and deprivation of BMPs leads to reversal of dormancy and increase in proliferation of dormant cells. Role of BMPs in the dormancy-recurrence axis may offer a therapeutic approach to retain the disseminated CSCs in perpetual dormant state. Therefore, comprehensive understanding of the role of BMPs in various microenvironment of disseminated tumor cell is considered to open a new avenue for the treatment of cancer metastasis.

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Acknowledgement

This work was supported by the National Institutes of Health (grants R01CA124650 and R01CA129000 to K. Watabe) and the US Department of Defense (grant PC101369 to K. Watabe and grant PC094294 to F. Xing).

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Authors and Affiliations

  1. Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA

    Sambad Sharma, Fei Xing & Kounosuke Watabe

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  1. Sambad Sharma
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  2. Fei Xing
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  3. Kounosuke Watabe
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Correspondence to Kounosuke Watabe .

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Editors and Affiliations

  1. Department of Biological Sciences, Kean University, Room 213, Library Building, Union, New Jersey, USA

    M.A. Hayat

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Sharma, S., Xing, F., Watabe, K. (2014). Dormancy and Recurrence of Cancer Stem Cells in Bone: Role of Bone Morphogenetic Proteins. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 2. Tumor Dormancy and Cellular Quiescence and Senescence, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7726-2_27

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