Microenvironments Dictating Tumor Cell Dormancy

  • Paloma Bragado
  • Maria Soledad Sosa
  • Patricia Keely
  • John Condeelis
  • Julio A. Aguirre-Ghiso
Chapter

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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Paloma Bragado
    • 1
  • Maria Soledad Sosa
    • 1
  • Patricia Keely
    • 2
  • John Condeelis
    • 3
  • Julio A. Aguirre-Ghiso
    • 1
    • 4
  1. 1.Division of Hematology and Oncology, Department of Medicine, Department of OtolaryngologyMount Sinai School of Medicine, Tisch Cancer Institute, Black Family Stem Cell InstituteNew YorkUSA
  2. 2.Laboratory for Cellular and Molecular Biology, Department of Cell and Regenerative Biology University of Wisconsin-Madison, R. M. Bock LaboratoriesMadisonUSA
  3. 3.Department of Anatomy and Structural BiologyGruss Lipper Biophotonics Center, Albert Einstein Cancer Center, Tumor Microenvironment and Metastasis ProgramNew YorkUSA
  4. 4.Division of Hematology and Oncology, Department of Medicine, Department of Otolaryngology, Head and Neck Cancer Research ProgramMount Sinai School of MedicineNew YorkUSA

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