Proximity of Metastatic Cells Enhances Their Mechanobiological Invasiveness
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A critical step in metastases formation is cancer-cell invasion through tissue. During invasion, cells change morphology and apply forces to their surroundings. We have previously shown that single, metastatic breast-cancer cells will mechanically indent a synthetic, impenetrable polyacrylamide gel with physiological-stiffness in attempted invasion; benign breast cells do not indent the gels. In solid tumors, e.g., breast cancers, metastases occur predominantly by collective cell-invasion. Thus, here we evaluate the effects of cell proximity on mechanical invasiveness, specifically through changes in gel indention. Gel indentation is induced by 56, 33 and 2% (in >1000 cells), respectively, of adjacent high metastatic potential (MP), low MP and benign breast cells, being double the amounts observed in single, well-separated cells. Single cells exhibited a distribution of indentation depths below 10 µm, while adjacent cells also showed a second peak of deeper indentations. The second peak included 65% of indenting high MP cells as compared to 15% in the low MP cells, illustrating the difference in their invasiveness. Thus, proximity of the metastatic cells enhances their mechanical ability to invade, demonstrating why collective cancer-cell migration is likely more efficient. This could potentially provide a rapid, quantitative approach to identify metastatic cells, and to determine their metastatic potential.
KeywordsMechanobiology In vitro invasiveness Metastatic potential Cell-substrate mechanical interactions Breast cancer
The authors thank Mrs. Rakefet Rozen for her assistance in analyzing the results. The work was partially supported by The Technion EVPR Funds—The Elias Fund for Medical Research and The Karbeling Fund for Bio-Medical Engineering Research, and also by a grant from the Ministry of Science, Technology and Space, Israel, and the National Science Council (NSC) of Taiwan.
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