PT  - JOURNAL ARTICLE
AU  - Sarah Alshehri
AU  - Tonja Pavlovič
AU  - Sadaf Farsinejad
AU  - Panteha Behboodi
AU  - Li Quan
AU  - Daniel Centeno
AU  - Douglas Kung
AU  - Marta Rezler
AU  - Woo Lee
AU  - Piotr Jasiński
AU  - Elżbieta Dziabaszewska
AU  - Ewa Nowak-Markwitz
AU  - Dilhan Kalyon
AU  - Mikołaj P. Zaborowski
AU  - Marcin Iwanicki
TI  - Extracellular Matrix Modulates Outgrowth Dynamics in Ovarian Cancer
AID  - 10.1101/2022.01.30.478322
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.30.478322
4099  - http://biorxiv.org/content/early/2022/08/22/2022.01.30.478322.short
4100  - http://biorxiv.org/content/early/2022/08/22/2022.01.30.478322.full
AB  - Ovarian carcinoma (OC) forms outgrowths that extend from the outer surface of an afflicted organ into the peritoneum. OC outgrowth formation is poorly understood because there is limited availability of OC cell culture models to examine the behavior of cell assemblies that form outgrowths. Prompted by immunochemical evaluation of extracellular matrix (ECM) components, laminin γ1 and collagens, in human tissues representing untreated and chemotherapy-recovered OC, we developed laminin- and collagen-rich ECM-reconstituted cell culture models amenable to studies of cell clusters that can form outgrowths. We demonstrate that ECM promotes outgrowth formation in fallopian tube non-ciliated epithelial cells (FNE) expressing mutant p53-R175H and various OC cell lines. Outgrowths were initiated by cells that had undergone outward translocation and, upon mechanical detachment, could intercalate into mesothelial cell monolayers. Electron microscopy, optical coherence tomography (OCT), and small amplitude oscillatory shear experiments revealed that high ECM concentration increased ECM fibrous network thickness and led to high shear elasticity in the ECM environment. These physical characteristics were associated with the suppression of outgrowths. A culture environment with low ECM concentration mimicked viscoelasticity of malignant peritoneal fluids (ascites) and supported cell proliferation, cell translocation, and outgrowth formation. These results highlight the importance of ECM microenvironments in modulating OC growth and could provide an additional explanation of why primary and recurrent ovarian tumors form outgrowths that protrude into the peritoneal cavity.Competing Interest StatementThe authors have declared no competing interest.