Cancer burden is controlled by mural cell-β3-integrin regulated crosstalk with tumor cells

Wong, Ping-Pui, Munoz-Felix, Jose M, Hijazi, Maruan, Kim, Hyojin, Robinson, Stephen, De Luxan-Delgado, Beatriz, Rodiguez-Hernandez, Irene, Maiques, Oscar, Meng, Ya-Ming, Meng, Qiong, Bodrug, Natalia, Dukinfield, Matthew Scott, Reynolds, Louise E, Elia, George, Clear, Andrew, Harwood, Catherine, Wang, Yu, Campbell, James J, Singh, Rajinder, Zhang, Penglie, Schall, Thomas J, Matchett, Kylie P, Henderson, Neil, Szlosarek, Peter W, Dreger, Sally, Smith, Sally, Jones, J Louise, Gribben, John G, Cutillas, Pedro R, Meier, Pascal, Sanz-Moreno, Victoria and Hodivala-Dilke, Kairbaan (2020) Cancer burden is controlled by mural cell-β3-integrin regulated crosstalk with tumor cells. Cell, 181 (6). 1346-1363.e21. ISSN 0092-8674

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Abstract

Enhanced blood vessel (BV) formation is thought to drive tumor growth through elevated nutrient delivery. However, this observation has overlooked potential roles for mural cells in directly affecting tumor growth independent of BV function. Here we provide clinical data correlating high percentages of mural-β3-integrin-negative tumor BVs with increased tumor sizes but no effect on BV numbers. Mural-β3-integrin loss also enhances tumor growth in implanted and autochthonous mouse tumor models with no detectable effects on BV numbers or function. At a molecular level, mural-cell β3-integrin loss enhances signaling via FAK-p-HGFR-p-Akt-p-p65, driving CXCL1, CCL2, and TIMP-1 production. In particular, mural-cell-derived CCL2 stimulates tumor cell MEK1-ERK1/2-ROCK2-dependent signaling and enhances tumor cell survival and tumor growth. Overall, our data indicate that mural cells can control tumor growth via paracrine signals regulated by β3-integrin, providing a previously unrecognized mechanism of cancer growth control.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: LivePure Connector
Date Deposited: 02 Jun 2020 00:15
Last Modified: 20 Aug 2020 01:07
URI: https://ueaeprints.uea.ac.uk/id/eprint/75425
DOI: 10.1016/j.cell.2020.02.003

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