title: Contribution of soft substrates to malignancy and tumor suppression during colon cancer cell division.
abstract: In colon cancer, a highly aggressive disease, progression through the malignant sequence is accompanied by increasingly numerous chromosomal rearrangements. To colonize target organs, invasive cells cross several tissues of various elastic moduli. Whether soft tissue increases malignancy or in contrast limits invasive colon cell spreading remains an open question. Using polyelectrolyte multilayer films mimicking microenvironments of various elastic moduli, we revealed that human SW480 colon cancer cells displayed increasing frequency in chromosomal segregation abnormalities when cultured on substrates with decreasing stiffness. Our results show that, although decreasing stiffness correlates with increased cell lethality, a significant proportion of SW480 cancer cells did escape from the very soft substrates, even when bearing abnormal chromosome segregation, achieve mitosis and undergo a new cycle of replication in contrast to human colonic HCoEpiC cells which died on soft substrates. This observation opens the possibility that the ability of cancer cells to overcome defects in chromosome segregation on very soft substrates could contribute to increasing chromosomal rearrangements and tumor cell aggressiveness.
authors.affiliation: Inserm UMR 1121, Strasbourg, France ; Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France ; Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Rabineau
authors.forename: Leyla
authors.initials: L
authors.lastname: Kocgozlu
authors.forename: Denis
authors.initials: D
authors.lastname: Dujardin
authors.forename: Bernard
authors.initials: B
authors.lastname: Senger
authors.forename: Youssef
authors.initials: Y
authors.lastname: Haikel
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Voegel
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Freund
authors.forename: Pierre
authors.initials: P
authors.lastname: Schaaf
authors.forename: Philippe
authors.initials: P
authors.lastname: Lavalle
authors.forename: Dominique
authors.initials: D
authors.lastname: Vautier
mesh_terms: D002453:Cell Cycle; D016923:Cell Death; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004548:Elasticity; D006801:Humans; D059016:Tumor Microenvironment