Tumor macrophages are pivotal constructors of tumor collagenous matrix.
Tumor macrophages are pivotal constructors of tumor collagenous matrix.
复制标题
DOI：
10.1084/jem.20151193
复制
发表时间：
2016-10-17
期刊：
影响因子：
--
通讯作者：
Varol C
中科院分区：
文献类型：
--
作者：
Afik R;Zigmond E;Vugman M;Klepfish M;Shimshoni E;Pasmanik-Chor M;Shenoy A;Bassat E;Halpern Z;Geiger T;Sagi I;Varol C
肿瘤相关巨噬细胞是肿瘤ECM结构和分子组成的关键构建者。特别是，它们协调了致瘤性胶原ECM小生境的建立。肿瘤相关巨噬细胞（TAM）通过多种机制促进肿瘤的发展、侵袭和扩散。在这项研究中，使用原位结直肠癌（CRC）模型，我们发现单核细胞衍生的TAM通过重塑其细胞外基质（ECM）的组成和结构来促进肿瘤的发展。（a）TAM丰富和缺乏的肿瘤组织和（B）分选的肿瘤相关和驻留的结肠巨噬细胞亚群的无偏转录组学和蛋白质组学分析定义了由它们提供给肿瘤微环境的基质细胞蛋白和重塑酶的集合组成的独特的TAM诱导的ECM分子特征。值得注意的是，这些ECM蛋白中的许多在人CRC中相对于健康结肠特异性增加。具体来说，我们证明，虽然分化成TAM，单核细胞上调与胶原ECM，特别是胶原I型，VI型和XIV的合成和组装相关的基质重塑程序。通过先进的成像技术进一步证实了这一发现，显示TAM在肿瘤发展过程中指导胶原纤维的沉积、交联和线性化，特别是在肿瘤侵袭区域。最后，我们表明，癌症相关的成纤维细胞显着超过TAM在这个模型中，他们的胶原蛋白XIV和I的表达减少TAM缺乏。在这里，我们概述了一种新的TAM与胶原ECM小生境的建设相关的促肿瘤功能。
Tumor-associated macrophages are pivotal constructors of the tumoral ECM structure and molecular composition. In particular, they orchestrate the buildup of the tumorigenic collagenous ECM niche. Tumor-associated macrophages (TAMs) promote tumor development, invasion, and dissemination by various mechanisms. In this study, using an orthotopic colorectal cancer (CRC) model, we found that monocyte-derived TAMs advance tumor development by the remodeling of its extracellular matrix (ECM) composition and structure. Unbiased transcriptomic and proteomic analyses of (a) TAM-abundant and -deficient tumor tissues and (b) sorted tumor-associated and -resident colonic macrophage subpopulations defined a distinct TAM-induced ECM molecular signature composed of an ensemble of matricellular proteins and remodeling enzymes they provide to the tumor microenvironment. Remarkably, many of these ECM proteins are specifically increased in human CRC versus healthy colon. Specifically, we demonstrate that although differentiating into TAMs, monocytes up-regulate matrix-remodeling programs associated with the synthesis and assembly of collagenous ECM, specifically collagen types I, VI, and XIV. This finding was further established by advanced imaging showing that TAMs instruct the deposition, cross-linking, and linearization of collagen fibers during tumor development, especially at areas of tumor invasiveness. Finally, we show that cancer-associated fibroblasts are significantly outnumbered by TAMs in this model and that their expression of collagen XIV and I is reduced by TAM deficiency. Here, we outline a novel TAM protumoral function associated with building of the collagenous ECM niche.
登录
查看更多内容
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
11.2
作者：
Movahedi, Kiavash;Laoui, Damya;Van Ginderachter, Jo A.
通讯作者：
Van Ginderachter, Jo A.
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
32.4
作者：
Knipper JA;Willenborg S;Brinckmann J;Bloch W;Maaß T;Wagener R;Krieg T;Sutherland T;Munitz A;Rothenberg ME;Niehoff A;Richardson R;Hammerschmidt M;Allen JE;Eming SA
通讯作者：
Eming SA
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO