Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 11;181(6):1346-1363.e21.
doi: 10.1016/j.cell.2020.02.003. Epub 2020 May 29.

Cancer Burden Is Controlled by Mural Cell-β3-Integrin Regulated Crosstalk with Tumor Cells

Ping-Pui Wong  1 , José M Muñoz-Félix  2 , Maruan Hijazi  3 , Hyojin Kim  4 , Stephen D Robinson  5 , Beatriz De Luxán-Delgado  6 , Irene Rodríguez-Hernández  7 , Oscar Maiques  7 , Ya-Ming Meng  8 , Qiong Meng  8 , Natalia Bodrug  6 , Matthew Scott Dukinfield  6 , Louise E Reynolds  6 , George Elia  6 , Andrew Clear  3 , Catherine Harwood  9 , Yu Wang  10 , James J Campbell  10 , Rajinder Singh  10 , Penglie Zhang  10 , Thomas J Schall  10 , Kylie P Matchett  11 , Neil C Henderson  11 , Peter W Szlosarek  12 , Sally A Dreger  6 , Sally Smith  6 , J Louise Jones  6 , John G Gribben  3 , Pedro R Cutillas  3 , Pascal Meier  4 , Victoria Sanz-Moreno  7 , Kairbaan M Hodivala-Dilke  13
Affiliations
Free article

Cancer Burden Is Controlled by Mural Cell-β3-Integrin Regulated Crosstalk with Tumor Cells

Ping-Pui Wong et al. Cell. .
Free article

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.

Keywords: mural cell; paracrine; β3-integrin.

PubMed Disclaimer

Conflict of interest statement

Declaration of Interests J.J.C., Y.W., R.S., T.J.S., and P.Z. are employees of ChemoChentryx. They developed and provided the CCR2 inhibitor used in this study.

Publication types