title: Attenuation of cell mechanosensitivity in colon cancer cells during in vitro metastasis.
abstract: 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.
authors.affiliation: Department of Mechanical Science and Engineering, College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wen
authors.forename: Theresa B
authors.initials: TB
authors.lastname: Kuhlenschmidt
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kuhlenschmidt
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
authors.forename: Taher A
authors.initials: TA
authors.lastname: Saif
mesh_terms: D002448:Cell Adhesion; D002452:Cell Count; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D040542:Mechanotransduction, Cellular; D013499:Surface Properties