| Literature DB >> 32473126 |
Ping-Pui Wong1, José M Muñoz-Félix2, Maruan Hijazi3, Hyojin Kim4, Stephen D Robinson5, Beatriz De Luxán-Delgado6, Irene Rodríguez-Hernández7, Oscar Maiques7, Ya-Ming Meng8, Qiong Meng8, Natalia Bodrug6, Matthew Scott Dukinfield6, Louise E Reynolds6, George Elia6, Andrew Clear3, Catherine Harwood9, Yu Wang10, James J Campbell10, Rajinder Singh10, Penglie Zhang10, Thomas J Schall10, Kylie P Matchett11, Neil C Henderson11, Peter W Szlosarek12, Sally A Dreger6, Sally Smith6, J Louise Jones6, John G Gribben3, Pedro R Cutillas3, Pascal Meier4, Victoria Sanz-Moreno7, Kairbaan M Hodivala-Dilke13.
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.Entities:
Keywords: mural cell; paracrine; β3-integrin
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Year: 2020 PMID： 32473126 DOI： 10.1016/j.cell.2020.02.003
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582