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 ® 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. From Xin Tang’s recent
Xin Tang is currently a PH. D. candidate of Mechanical Science and Engineering Department at U of I-Urbana and Champaign. He earned a bachelor degree (with honor) from University of Science and Technology of China (USTC) in 2003, majoring in Theoretical and Applied Mechanics, with advisors of Prof. Shipping He and Prof. Boqing Xu. Xin Tang earned his Master degree from Case Western Reserve University, USA, in 2006, major in both Mechanical Engineering and Materials Science, with advisors of Prof. Vikas Prakash and Prof. John Lewandowski. His current research focuses on the effect of the mechanical elasticity of micro-environment on cancer metastasis, with advisors of Prof. Taher Saif (MechSE) and Prof. Mark Kuhlenschmidt (pathibiology). Xin Tang's career goal is to be a leader in the cell mechanics field and an excellent teacher to foster the new generations of scientists.
From Xin Tang's Trainee profile
Midwest Cancer Nanotechnology Traning Center (M-CNTC) Training the next generation of leaders who will define the new frontiers and applications of nanotechnology in cancer research It is known that more than 1.5 million Americans were diagnosed with cancer during 2010, and half a million have died (Cancer Statistics 2010, ACS). In spite of considerable effort, there has been limited success in reducing per capita deaths from cancer since 1950. This calls for a paradigm shift in the understanding, detection, and intervention of the evolution of cancer from a single cell to tumor scale.
In response to this challenge the M-CNTC has assembled a preeminent interdisciplinary team of researchers and educators across the University of Illinois and clinical collaborators in the Midwest to train the next generation of engineers, physical scientists, and biologists to address the challenge of understanding, managing, diagnosing, and treating cancer using the most recent advancements in nanotechnology.
Cellular and Molecular Mechanics and Bionanotechnology (CMMB-IGERT) Training the next generation of leaders who will define the new frontiers of cellular and molecular mechanics and bionanotechnology Critical experiments during the last decade show a fundamental link between the micro- and macro-mechanical environment (i.e., intracellular forces, local shear, gravitational force) and a variety of cell functionalities, their lineage, and phenotype. These findings pose the grand challenge: what is the underlying molecular mechanism that cells employ to transduce mechanical signals to biochemical pathways?
In response to this challenge the CMMB IGERT launched an interdisciplinary research effort with national and international collaborators.