Effects of Tumor Necrosis Factor-α on Morphology and Mechanical Properties of HCT116 Human Colon Cancer Cells Investigated by Atomic Force Microscopy

Chronic inflammation orchestrates the tumor microenvironment and is strongly associated with cancer. Tumor necrosis factor-alpha (TNF alpha) is involved in tumor invasion and metastasis by inducing epithelial to mesenchymal transition (EMT). This process is defined by the loss of epithelial characteristics and gain of mesenchymal traits. The mechanisms of TNF alpha-induced EMT in cancer cells have been well studied. However, mechanical properties have not yet been probed. In this work, atomic force microscopy (AFM) was applied to investigate the morphology and mechanical properties of EMT in HCT116 human colon cancer cells. A remarkable morphological change from cobblestone shape to spindle-like morphology was observed. In parallel, AFM images showed that the cellular cytoskeleton was rearranged from a cortical to a stress-fiber pattern. Moreover, cell stiffness measurements indicated that Young's modulus of cells gradually reduced from 1 to 3 days with TNF alpha-treatment, but it has an apparent increase after 4 days of treatment compared with that for 3 days. Additionally, Young's modulus of the cells treated with TNF alpha for 4 days is slightly larger than that for 1 or 2 days, but still less than that of the untreated cells. Our work contributes to a better understanding of colorectal cancer metastasis induced by inflammation.