TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Holle, Andrew A1 - Devi, Neethu Govindan Kutty A1 - Clar, Kim A1 - Fan, Anthony A1 - Saif, Taher A1 - Kemkemer, Ralf A1 - Spatz, Joachim T1 - Cancer cells invade confined microchannels via a self-directed mesenchymal-to-amoeboid transition JF - Nano letters : a journal dedicated to nanoscience and nanotechnology N2 - Cancer cell invasion through physical barriers in the extracellular matrix (ECM) requires a complex synergy of traction force against the ECM, mechanosensitive feedback, and subsequent cytoskeletal rearrangement. PDMS microchannels were used to investigate the transition from mesenchymal to amoeboid invasion in cancer cells. Migration was faster in narrow 3 μm-wide channels than in wider 10 μm channels, even in the absence of cell-binding ECM proteins. Cells permeating narrow channels exhibited blebbing and had smooth leading edge profiles, suggesting an ECM-induced transition from mesenchymal invasion to amoeboid invasion. Live cell labeling revealed a mechanosensing period in which the cell attempts mesenchymal-based migration, reorganizes its cytoskeleton, and proceeds using an amoeboid phenotype. Rho/ROCK (amoeboid) and Rac (mesenchymal) pathway inhibition revealed that amoeboid invasion through confined environments relies on both pathways in a time- and ECM dependent manner. This demonstrates that cancer cells can dynamically modify their invasion programming to navigate physically confining matrix conditions. KW - cancer cell invasion KW - mechanobiology KW - microchannels KW - confined migration Y1 - 2019 UN - https://nbn-resolving.org/urn:nbn:de:bsz:rt2-opus4-23924 SN - 1530-6984 SS - 1530-6984 U6 - https://doi.org/10.1021/acs.nanolett.8b04720 DO - https://doi.org/10.1021/acs.nanolett.8b04720 VL - 19 IS - 4 SP - 2280 EP - 2290 S1 - 11 PB - American Chemical Society CY - Washington, DC ER -