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Topological defects in the mesothelium suppress ovarian cancer cell clearance

APL Bioengineering, ISSN: 2473-2877, Vol: 5, Issue: 3, Page: 036103
2021
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Experimental model of ovarian cancer shows effect of healthy cell arrangement in metastasis

A key element to slowing metastasis in ovarian cancer is understanding the mechanisms of how tumor cells invade tissues. Biophysics researchers explain how microscopic defects in how healthy cells line up can alter how easily ovarian cancer cells invade tissue. Using an experimental model, the group found that disruptions in the normal cellular layout, called topological defects, affect the rate o

Article Description

We investigated an in vitro model for mesothelial clearance, wherein ovarian cancer cells invade into a layer of mesothelial cells, resulting in mesothelial retraction combined with cancer cell disaggregation and spreading. Prior to the addition of tumor cells, the mesothelial cells had an elongated morphology, causing them to align with their neighbors into well-ordered domains. Flaws in this alignment, which occur at topological defects, have been associated with altered cell density, motion, and forces. Here, we identified topological defects in the mesothelial layer and showed how they affected local cell density by producing a net flow of cells inward or outward, depending on the defect type. At locations of net inward flow, mesothelial clearance was impeded. Hence, the collective behavior of the mesothelial cells, as governed by the topological defects, affected tumor cell clearance and spreading. Importantly, our findings were consistent across multiple ovarian cancer cell types, suggesting a new physical mechanism that could impact ovarian cancer metastasis.

Bibliographic Details

Zhang, Jun; Yang, Ning; Kreeger, Pamela K; Notbohm, Jacob

AIP Publishing

Chemical Engineering; Biochemistry, Genetics and Molecular Biology; Materials Science; Engineering

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