title: Proximity of Metastatic Cells Enhances Their Mechanobiological Invasiveness.
abstract: 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.
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 3200003, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Merkher
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 3200003, Israel. daphnew@technion.ac.il.
authors.forename: Daphne
authors.identifier: 0000-0002-9670-3418
authors.initials: D
authors.lastname: Weihs
mesh_terms: D000180:Acrylic Resins; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D055119:Elastic Modulus; D006801:Humans; D020100:Hydrogels; D009361:Neoplasm Invasiveness; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D020100:Hydrogels; D000099166:Polyacrylamides
keywords: Breast cancer; Cell-substrate mechanical interactions; In vitro invasiveness; Mechanobiology; Metastatic potential