Abstract
The mechanisms driving dormancy of disseminated tumor cells (DTCs) remain largely unknown. Here, we discuss experimental evidence and theoretical frameworks that support three potential scenarios contributing to tumor cell dormancy. The first scenario proposes that DTCs from invasive cancers activate stress signals in response to the dissemination process and/or a growth suppressive target organ microenvironment inducing dormancy. The second scenario asks whether therapy and/or micro-environmental stress conditions (e.g. hypoxia) acting on primary tumor cells carrying specific gene signatures prime new DTCs to enter dormancy in a matching target organ microenvironment that can also control the timing of DTC dormancy. The third and final scenario proposes that early dissemination contributes a population of DTCs that are unfit for immediate expansion and survive mostly in an arrested state well after primary tumor surgery, until genetic and/or epigenetic mechanisms activate their proliferation. We propose that DTC dormancy is ultimately a survival strategy that when targeted will eradicate dormant DTCs preventing metastasis. For these non-mutually exclusive scenarios we review experimental and clinical evidence in their support.
Keywords
- Epithelial Mesenchymal Transition
- Atypical Ductal Hyperplasia
- Disseminate Tumor Cell
- Discoidin Domain Receptor
- Metastatic Growth
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Paloma Bragado and Maria Soledad Sosa contributed equally to this work.
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Acknowledgments
This work is supported by grants from the Samuel Waxman Cancer Research Foundation Tumor Dormancy Program, NIH/National Cancer Institute (CA109182), NIEHS (ES017146) and NYSTEM to J.A.A-G.
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Bragado, P., Sosa, M.S., Keely, P., Condeelis, J., Aguirre-Ghiso, J.A. (2012). Microenvironments Dictating Tumor Cell Dormancy. In: Ignatiadis, M., Sotiriou, C., Pantel, K. (eds) Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer. Recent Results in Cancer Research, vol 195. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28160-0_3
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