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Microenvironments Dictating Tumor Cell Dormancy

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Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 195))

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.

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.

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Department of Otolaryngology, Mount Sinai School of Medicine, Tisch Cancer Institute, Black Family Stem Cell Institute, New York, NY, USA

    Paloma Bragado, Maria Soledad Sosa & Julio A. Aguirre-Ghiso

  2. Laboratory for Cellular and Molecular Biology, Department of Cell and Regenerative Biology, University of Wisconsin-Madison, R. M. Bock Laboratories, Room 227D 1525 Linden Drive, Madison, WI, 53706, USA

    Patricia Keely

  3. Department of Anatomy and Structural Biology, Gruss Lipper Biophotonics Center, Albert Einstein Cancer Center, Tumor Microenvironment and Metastasis Program, New York, NY, USA

    John Condeelis

  4. Division of Hematology and Oncology, Department of Medicine, Department of Otolaryngology, Head and Neck Cancer Research Program, Mount Sinai School of Medicine, New York, NY, 10029, Box:1079, USA

    Julio A. Aguirre-Ghiso

Authors
  1. Paloma Bragado
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  2. Maria Soledad Sosa
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  3. Patricia Keely
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  4. John Condeelis
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  5. Julio A. Aguirre-Ghiso
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Correspondence to Julio A. Aguirre-Ghiso .

Editor information

Editors and Affiliations

  1. , Breast Cancer Translational Res. Lab., Institut Jules Bordet, Boulevard de Waterloo 125, Brussels, 1000, Belgium

    Michail Ignatiadis

  2. , Breast Cancer Translational Res. Lab., Institut Jules Bordet, Boulevard de Waterloo 125, Brussels, 1000, Belgium

    Christos Sotiriou

  3. Zentrum für Experimentelle Medizin, Inst. Tumorbiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, Hamburg, 20246, Germany

    Klaus Pantel

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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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  • DOI: https://doi.org/10.1007/978-3-642-28160-0_3

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