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.
Highlights
Over the last 10 years, it has become evident that cell behaviour depends on chemical cues but that mechanical properties of cellular environment play an as important role
Using polyelectrolyte multilayers films (PEM) [14,15,16,17,18], we revealed that human SW480 colon cancer cells displayed increasing frequency in chromosomal segregation abnormalities when cultured on substrates with decreasing stiffness (Figure 1) and [3]
To determine whether tumor cells are able to progress through mitosis on very soft substrates, SW480 cells, synchronized using the mitotic shake-off method, were seeded on PEM films with decreasing stiffness (Young moduli decreasing from 50 down to 0 kPa, Table 1) and followed by live-cell imaging during 2h30
Summary
Over the last 10 years, it has become evident that cell behaviour depends on chemical cues but that mechanical properties of cellular environment play an as important role This was spectacularly demonstrated by the landmark experiments of Discher’s group who showed that mesenchymal stem cells can either differentiate into osteoblasts, fibroblasts or neurons depending upon the Young modulus of the adhesion substrate [1]. Osteoblasts require Young moduli in the range of MPa to adhere whereas fibroblasts adhere on softer substrates whose moduli of about 10 kPa [2] and neurons grow on extremely soft substrates of about 1 kPa [1] These distinctive values are in accordance to the Young moduli that characterize the tissues surrounding these different cell types. Soft substrates (below 50 kPa) were described as a physical microenvironment barrier almost completely inhibiting the PtK2 cells [3]
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