Contribution of soft substrates to malignancy and tumor suppression during colon cancer cell division

• Published in: PloS one Vol. 8; no. 10; p. e78468
• Main Authors: Rabineau, Morgane, Kocgozlu, Leyla, Dujardin, Denis, Senger, Bernard, Haikel, Youssef, Voegel, Jean-Claude, Freund, Jean-Noel, Schaaf, Pierre, Lavalle, Philippe, Vautier, Dominique
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.10.2013; Public Library of Science (PLoS)
• Subjects: Abnormalities; Cancer; Cell Cycle; Cell Death; Cell division; Cell Line, Tumor; Cell spreading; Chromosome Aberrations; Chromosome rearrangements; Chromosomes; Colon; Colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Defects; Elastic limit; Elasticity; Fibroblasts; Humans; Invasiveness; Lethality; Life Sciences; Malignancy; Mechanical properties; Metastasis; Microenvironments; Mimicry; Mitosis; Modulus of elasticity; Organs; Polyelectrolytes; Stem cells; Stiffness; Substrates; Surface chemistry; Tissues; Tumor Microenvironment; Tumor suppression; Tumors; France; Singapore
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078468

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.