Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue.
Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue.
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DOI：
10.1158/1541-7786.mcr-12-0307
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Diamandis EP
中科院分区：
文献类型：
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作者：
Karagiannis GS;Poutahidis T;Erdman SE;Kirsch R;Riddell RH;Diamandis EP
肿瘤细胞通过各种生长因子和细胞因子招募成纤维细胞。这些“癌症相关成纤维细胞”(CAF)积极地与肿瘤细胞相互作用，形成肌成纤维细胞微环境，促进癌症生长和存活，并支持恶性肿瘤。他们的旁分泌信号系统中的几种产品已被认为是肿瘤生长和转移的调节剂。然而，促进肿瘤的细胞信号并不是使CAF成为“肿瘤微环境”的关键组成部分的唯一原因，因为CAF同时影响发展中的肿瘤的结构和生长机制。CAF参与了肿瘤周围间质的重塑，这是肿瘤细胞侵袭、扩张和转移的先决条件。CAF不是以单个细胞的形式出现在肿瘤周围，但它们的作用是完全部署一个促结缔组织程序，其特征是“合胞”(或集体)构型和改变的细胞黏附特性。这样的肌成纤维细胞群让人想起在伤口愈合过程中遇到的那些。“癌症是一种无法愈合的伤口”的观点导致了伤口愈合和肿瘤形成之间的有用比较，并扩大了我们对CAF队列在癌症中的作用的了解。在这个肿瘤侵袭和转移的综合模型中，我们认为CAF支持的微环境具有双重的促肿瘤作用。它不仅为癌细胞的去分化、增殖和存活提供必要的信号，而且还促进癌细胞的局部侵袭和转移现象。
Neoplastic cells recruit fibroblasts through various growth factors and cytokines. These “cancer-associated fibroblasts” (CAF) actively interact with neoplastic cells and form a myofibroblastic microenvironment that promotes cancer growth and survival and supports malignancy. Several products of their paracrine signaling repertoire have been recognized as tumor growth and metastasis regulators. However, tumor-promoting cell signaling is not the only reason that makes CAFs key components of the “tumor microenvironment,” as CAFs affect both the architecture and growth mechanics of the developing tumor. CAFs participate in the remodeling of peritumoral stroma, which is a prerequisite of neoplastic cell invasion, expansion, and metastasis. CAFs are not present peritumorally as individual cells but they act orchestrated to fully deploy a desmoplastic program, characterized by “syncytial” (or collective) configuration and altered cell adhesion properties. Such myofibroblastic cohorts are reminiscent of those encountered in wound-healing processes. The view of “cancer as a wound that does not heal” led to useful comparisons between wound healing and tumorigenesis and expanded our knowledge of the role of CAF cohorts in cancer. In this integrative model of cancer invasion and metastasis, we propose that the CAF-supported microenvironment has a dual tumor-promoting role. Not only does it provide essential signals for cancer cell dedifferentiation, proliferation, and survival but it also facilitates cancer cell local invasion and metastatic phenomena.