Inserm UMR 1121, Strasbourg, France ; Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France ; Fédération de Médecine Translationnelle, Strasbourg, France.
PLoS One. 2013 Oct 22;8(10):e78468. doi: 10.1371/journal.pone.0078468. eCollection 2013.
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.
在结肠癌这一高度侵袭性疾病中，恶性进展伴随着越来越多的染色体重排。为了在靶器官中定植，侵袭性细胞需要穿过不同弹性模量的多种组织。软组织是否会增加恶性程度，还是相反会限制侵袭性结肠细胞的扩散，这仍是一个悬而未决的问题。我们使用聚电解质多层膜模拟各种弹性模量的微环境，揭示了在弹性模量降低的基底上培养时，人 SW480 结肠癌细胞的染色体分离异常频率增加。我们的结果表明，尽管硬度降低与细胞致死率增加相关，但尽管存在染色体分离异常，仍有相当比例的 SW480 癌细胞能够从非常软的基底中逃逸，实现有丝分裂，并开始新的复制周期，而人结肠 HCoEpiC 细胞则会在软质基底上死亡。这一观察结果为一种可能性提供了依据，即癌细胞在非常软的基底上克服染色体分离缺陷的能力可能有助于增加染色体重排和肿瘤细胞的侵袭性。
