Ovarian cancer spheroids use myosin-generated force to clear the mesothelium.
Dissemination of ovarian tumors involves the implantation of cancer spheroids into the mesothelial monolayer on the walls of peritoneal and pleural cavity organs. Biopsies of tumors attached to peritoneal organs show that mesothelial cells are not present under tumor masses. We have developed a live, image-based in vitro model in which interactions between tumor spheroids and mesothelial cells can be monitored in real time to provide spatial and temporal understanding of mesothelial clearance. Here we provide evidence that ovarian cancer spheroids utilize integrin- and talin- dependent activation of myosin and traction force to promote mesothelial cells displacement from underneath a tumor cell spheroid. These results suggest that ovarian tumor cell clusters gain access to the sub-mesothelial environment by exerting force on the mesothelial cells lining target organs, driving migration and clearance of the mesothelial cells.
Department of Cell Biology, Harvard Medical School, Boston, 02115 MA, USA.
Marcin P
MP
Iwanicki
Rachel A
RA
Davidowitz
Mei Rosa
MR
Ng
Achim
A
Besser
Taru
T
Muranen
Melissa
M
Merritt
Gaudenz
G
Danuser
Tan A
TA
Ince
Tan
T
Ince
Joan S
JS
Brugge
D002448:Cell Adhesion / Q000502:physiology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010529:Peritoneal Cavity / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology*; D016608:Talin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D039081:Integrin alpha5beta1; C518832:TLN1 protein, human; D016608:Talin; D024462:Myosin Type II