A dormant state modulated by osmotic pressure controls clonogenicity of prostate cancer cells.
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 that 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, whereas 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.
Laboratoire de Biologie et de Pharmacologie Appliquée, Centre National de la Recherche Scientifique, UMR8113, Ecole Normale Supérieure de Cachan, 94235 Cachan Cedex, France.
Maryline
M
Havard
Laboratoire de Biologie et de Pharmacologie Appliquée, Centre National de la Recherche Scientifique, UMR8113, Ecole Normale Supérieure de Cachan, 94235 Cachan Cedex, France.
François
F
Dautry
Laboratoire de Biologie et de Pharmacologie Appliquée, Centre National de la Recherche Scientifique, UMR8113, Ecole Normale Supérieure de Cachan, 94235 Cachan Cedex, France. Electronic address: ttchenio@ens-cachan.fr.
Thierry
T
Tchénio
D028341:Activins / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism; D009995:Osmosis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D017077:Culture Media, Conditioned; D016159:Tumor Suppressor Protein p53; D028341:Activins