Attenuation of Cell Mechanosensitivity in Colon Cancer Cells during In Vitro MetastasisReport as inadecuate

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Human colon carcinoma HCT-8 cells show a stable transition from low to high metastatic state when cultured on appropriately soft substrates 21 kPa. Initially epithelial E in nature, the HCT-8 cells become rounded R after seven days of culture on soft substrate. R cells show a number of metastatic hallmarks 1. Here, we use gradient stiffness substrates, a bio-MEMS force sensor, and Coulter counter assays to study mechanosensitivity and adhesion of E and R cells. We find that HCT-8 cells lose mechanosensitivity as they undergo E-to-R transition. HCT-8 R cells- stiffness, spread area, proliferation and migration become insensitive to substrate stiffness in contrast to their epithelial counterpart. They are softer, proliferative and migratory on all substrates. R cells show negligible cell-cell homotypic adhesion, as well as non-specific cell-substrate adhesion. Consequently they show the same spread area on all substrates in contrast to E cells. Taken together, these results indicate that R cells acquire autonomy and anchorage independence, and are thus potentially more invasive than E cells. To the best of our knowledge, this is the first report of quantitative data relating changes in cancer cell adhesion and stiffness during the expression of an in vitro metastasis-like phenotype.

Author: Xin Tang, Qi Wen, Theresa B. Kuhlenschmidt, Mark S. Kuhlenschmidt, Paul A. Janmey , Taher A. Saif



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