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...
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| Veröffentlicht in: | Cancer discovery 2011-07, Vol.1 (2), p.144-157 |
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| container_title | Cancer discovery |
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| creator | Iwanicki, Marcin P Davidowitz, Rachel A Ng, Mei Rosa Besser, Achim Muranen, Taru Merritt, Melissa Danuser, Gaudenz Ince, Tan A Ince, Tan Brugge, Joan S |
| description | 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. |
| doi_str_mv | 10.1158/2159-8274.cd-11-0010 |
| format | Article |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Cell Adhesion - physiology Epithelium - metabolism Epithelium - pathology Female Fibronectins - metabolism Humans Integrin alpha5beta1 - metabolism Myosin Type II - metabolism Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Peritoneal Cavity - pathology Peritoneum - metabolism Peritoneum - pathology Spheroids, Cellular - metabolism Spheroids, Cellular - pathology Talin - metabolism Tumor Cells, Cultured |
| title | Ovarian cancer spheroids use myosin-generated force to clear the mesothelium |
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