Journal article
Mesothelial cells promote early Ovarian cancer metastasis through fibronectin secretion
HA Kenny, CY Chiang, EA White, EM Schryver, M Habis, IL Romero, A Ladanyi, CV Penicka, J George, K Matlin, A Montag, K Wroblewski, SD Yamada, AP Mazar, D Bowtell, E Lengyel
Journal of Clinical Investigation | Published : 2014
DOI: 10.1172/JCI74778
Abstract
Ovarian cancer (OvCa) metastasizes to organs in the abdominal cavity, such as the omentum, which are covered by a single layer of mesothelial cells. Mesothelial cells are generally thought to be "bystanders" to the metastatic process and simply displaced by OvCa cells to access the submesothelial extracellular matrix. Here, using organotypic 3D cultures, we found that primary human mesothelial cells secrete fbronectin in the presence of OvCa cells. Moreover, we evaluated the tumor stroma of 108 human omental metastases and determined that fbronectin was consistently overexpressed in these patients. Blocking fbronectin production in primary mesothelial cells in vitro or in murine models, eith..
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Awarded by National Institute of Child Health and Human Development
Funding Acknowledgements
We thank A.F. Haney (Department of Obstetrics and Gynecology, University of Chicago) for collecting omental biopsies, G. Isenberg (University of Chicago) for editing the manuscript, A. Mitra for helpful discussions, R. Fassler and S. Dallas for the Fn1<SUP>fl/fl</SUP> mice, S. Carbonell and OncoSynergy for providing the beta<INF>1</INF>, integrin antibody, K. Roby for providing the ID8 cell line, G.B. Mills for providing the HeyA8 and SKOV3ip1 cell lines, and the human tissue resource center (Terri Li and Lei-Ann Arceneaux) and flow cytometry (Ryan Duggan) core facilities at the University of Chicago for expert technical support. This work was supported by NCI grant R01 CA111882 and by an Ovarian Cancer Research Fund Program Project Development Grant to E. Lengyel. Finally, we appreciate all the patients, resident physicians, and attending physicians in the Department of Obstetrics and Gynecology at the University of Chicago for their commitment in collecting tissue.