A dormant state modulated by osmotic pressure controls clonogenicity of prostate cancer cells

LBPA, UMR8113 ENSC - CNRS, France.

 

Cell dormancy constitutes a limiting step of the metastatic process by preventing the proliferation of isolated cancer cells disseminated at distant sites from the primary tumor. The study of cancer cell dormancy is severely hampered by the lack of biological samples, so that the mechanisms which regulate cell dormancy have not been extensively explored. In this work, we describe the rapid induction in vitro of a dormant state in prostate cancer cells by exposure to a slightly hypertonic growth medium. This quiescence is observed only when cells are seeded at low density and, once established, requires additional stimuli besides osmotic pressure to be reversed. Media conditioned by cells grown at high density can partially prevent or reverse dormancy, a phenomenon which can be reproduced with citric acid. In addition to this role of small metabolites, inactivation of the p53 and smad pathways also counters the entry into dormancy while exposure to Activin A induces it to some extent. Thus, this easily inducible dormancy reproduces several features associated with the dormancy of stem cells and cancer cells in vivo.

Written by:
Havard M, Dautry F, Tchenio T.   Are you the author?

Reference: J Biol Chem. 2011 Oct 28. Epub ahead of print.

PubMed Abstract
PMID: 22039055

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