小柯机器人

壁细胞β3-整合素与肿瘤细胞的交流影响肿瘤负荷
2020-06-01 20:30
来源：小柯机器人

英国伦敦大学皇后玛丽学院Kairbaan M. Hodivala-Dilke、José M. Muñoz-Félix、中山大学Ping-Pui Wong等研究人员，合作发现壁细胞β3-整合素与肿瘤细胞的交流影响肿瘤负荷。这一研究成果于2020年5月29日在线发表在《细胞》上。

研究人员发现，高比例的壁细胞β3-整合素阴性肿瘤血管（BV）与肿瘤大小的增加相关，但对BV数量没有影响。壁细胞β3-整合素的丢失还可以促进植入和自体小鼠肿瘤模型中的肿瘤生长，而对BV数量或功能没有明显影响。在分子水平上，壁细胞β3-整合素的缺失通过FAK-p-HGFR-p-Akt-p-p65增强信号传导，从而驱动CXCL1、CCL2和TIMP-1的产生。
 
此外，源自壁细胞的CCL2刺激肿瘤细胞MEK1-ERK1/2-ROCK2依赖性信号传导并增强肿瘤细胞存活和肿瘤生长。总的来说，这些数据表明，壁细胞可以通过β3-整合素调节的旁分泌信号控制肿瘤的生长，从而提供了新的癌症生长控制机制。
 
据悉，人们认为血管（BV）形成的增强可通过增加营养输送来驱动肿瘤生长。然而，这一发现忽略了壁细胞在不依赖BV功能的情况下直接影响肿瘤生长的潜在作用。
 
附：英文原文

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

Author: Ping-Pui Wong, José M. Muoz-Félix, Maruan Hijazi, Hyojin Kim, Stephen D. Robinson, Beatriz De Luxán-Delgado, Irene Rodríguez-Hernández, Oscar Maiques, Ya-Ming Meng, Qiong Meng, Natalia Bodrug, Matthew Scott Dukinfield, Louise E. Reynolds, George Elia, Andrew Clear, Catherine Harwood, Yu Wang, James J. Campbell, Rajinder Singh, Penglie Zhang, Thomas J. Schall, Kylie P. Matchett, Neil C. Henderson, Peter W. Szlosarek, Sally A. Dreger, Sally Smith, J. Louise Jones, John G. Gribben, Pedro R. Cutillas, Pascal Meier, Victoria Sanz-Moreno, Kairbaan M. Hodivala-Dilke

Issue&Volume: 2020-05-29

Abstract: Enhanced blood vessel (BV) formation is thought to drive tumor growth through elevatednutrient delivery. However, this observation has overlooked potential roles for muralcells in directly affecting tumor growth independent of BV function. Here we provideclinical data correlating high percentages of mural-β3-integrin-negative tumor BVswith increased tumor sizes but no effect on BV numbers. Mural-β3-integrin loss alsoenhances tumor growth in implanted and autochthonous mouse tumor models with no detectableeffects on BV numbers or function. At a molecular level, mural-cell β3-integrin lossenhances 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-dependentsignaling and enhances tumor cell survival and tumor growth. Overall, our data indicatethat mural cells can control tumor growth via paracrine signals regulated by β3-integrin,providing a previously unrecognized mechanism of cancer growth control.

DOI: 10.1016/j.cell.2020.02.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30147-1

Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：66.85
官方网址：https://www.cell.com/
投稿链接：https://www.editorialmanager.com/cell/default.aspx

本期文章：《细胞》：Online/在线发表

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