Abstract
Although the role of stiffness on proliferative response of cancer cells has been well studied, little is known about the effect of topographic cues in guiding cancer cell proliferation. Here, we examined the effect of topographic cues on cancer cell proliferation using micron scale topographic features and observed that anisotropic features like microgratings at specific dimension could reduce proliferation of non-cancer breast epithelial cells (MCF-10A) but not that for malignant breast cancer cells (MDA-MB-231 and MCF-7). However, isotropic features such as micropillars did not affect proliferation of MCF-10A, indicating that the anisotropic environmental cues are essential for this process. Interestingly, acto-myosin contraction inhibitory drugs, Y-27632 and blebbistatin prevented micrograting-mediated inhibition on proliferation. Here, we propose the concept of Mechanically-Induced Dormancy (MID) where topographic cues could activate Rho-ROCK-Myosin signaling to suppress non-cancerous cells proliferation whereas malignant cells are resistant to this inhibitory barrier and therefore continue uncontrolled proliferation.
Highlights
From the primary tumor[13]
Pharmaceutical inhibitors against Rho-associated, coiled-coil containing protein kinase (ROCK) and myosin light chain kinase (MLCK) shows that migration of metastatic breast cancer cells, MDA-MB-231, along 3D collagen fiber is dependent on Rho- and ROCK-associated actomyosin contractility but not on MLCK signaling[15]
Prostate cancer cells preferentially migrate a greater distance along grooved topographies and the effect of topography is correlated with the metastatic potential of the cancer cells[17]
Summary
From the primary tumor[13]. Aligned collagen matrices promote cellular adhesion along the fibers and provide minimal resistance to migration, thereby enhancing directional persistence and displacement[14]. To investigate the effect of topographical cues on non-cancer and cancer cell proliferation, MCF-10A and MDA-MB-231 cells were cultured for 24 hours on different gratings coated with collagen matrix. In contrast to MCF-10A cells, there was no significant change in the rate of proliferation in MDA-MB-231 across the different gratings, which indicates that topographical cues reduce proliferation of only the normal epithelial but not that of metastatic breast cancer cells (Fig. 1b).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
