Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells.
Imaging of collectively invading cocultures of carcinoma cells and stromal fibroblasts reveals that the leading cell is always a fibroblast and that carcinoma cells move within tracks in the extracellular matrix behind the fibroblast. The generation of these tracks by fibroblasts is sufficient to enable the collective invasion of the squamous cell carcinoma (SCC) cells and requires both protease- and force-mediated matrix remodelling. Force-mediated matrix remodelling depends on integrins alpha3 and alpha5, and Rho-mediated regulation of myosin light chain (MLC) activity in fibroblasts, but these factors are not required in carcinoma cells. Instead, carcinoma cells use Cdc42 and MRCK (myotonic dystrophy kinase-related CDC42-binding protein kinases) mediated regulation of MLC to follow the tracks generated by fibroblasts.
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
Cedric
C
Gaggioli
Steven
S
Hooper
Cristina
C
Hidalgo-Carcedo
Robert
R
Grosse
John F
JF
Marshall
Kevin
K
Harrington
Erik
E
Sahai
D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002465:Cell Movement; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000502:physiology*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D039422:Integrin alpha3 / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D055551:HSP27 Heat-Shock Proteins; C442250:HSPB2 protein, human; D006360:Heat-Shock Proteins; D039422:Integrin alpha3; D039482:Integrin alpha5; D018994:Myosin Light Chains; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins