Han Yali, Zhang Yanwen, Jia Tanghong, Sun Yuping
Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, 250013, Shandong, China,
Tumour Biol. 2015 Mar;36(3):1385-94. doi: 10.1007/s13277-015-3230-8. Epub 2015 Feb 15.
Tumor microenvironment is composed of all the untransformed elements in the vicinity of tumor, mainly including a large number of stromal cells and extracellular matrix proteins, which play an active role in most solid tumor initiation and progression. Carcinoma-associated fibroblasts (CAFs), one of the most common stromal cell types in the tumor microenvironment, have been demonstrated to be involved in tumor growth, invasion, and metastasis. Therefore, they are becoming a promising target for anti-cancer therapies. In this review, we firstly summarize the current understandings of CAFs' molecular biology, including the heterogeneous cellular origins and molecular markers, and then, we focus on reviewing their various tumor-promoting phenotypes involved in complex mechanisms, which can be summarized to the CAF-conveyed paracrine signals in tumor cells, cancer stem cells, and metastasis-initiating cancer cells, as well as the CAF-enhanced extrinsic tumor-promoting processes including angiogenesis, extracellular matrix remodeling, and tumor-related inflammation; finally, we describe the available directions of CAF-based target therapy and suggest research areas which need to be further explored so as to deepen the understanding of tumor evolution and provide new therapeutic targets for cancer treatment.
肿瘤微环境由肿瘤附近所有未转化的成分组成，主要包括大量基质细胞和细胞外基质蛋白，它们在大多数实体瘤的发生和发展中发挥着积极作用。癌相关成纤维细胞（CAFs）是肿瘤微环境中最常见的基质细胞类型之一，已被证明参与肿瘤生长、侵袭和转移。因此，它们正成为抗癌治疗的一个有前景的靶点。在这篇综述中，我们首先总结了目前对CAFs分子生物学的认识，包括其异质性细胞起源和分子标志物，然后，我们重点回顾了它们参与复杂机制的各种促肿瘤表型，这些表型可概括为CAFs在肿瘤细胞、癌症干细胞和转移起始癌细胞中传递的旁分泌信号，以及CAFs增强的外在促肿瘤过程，包括血管生成、细胞外基质重塑和肿瘤相关炎症；最后，我们描述了基于CAFs的靶向治疗的可用方向，并提出了需要进一步探索的研究领域，以便加深对肿瘤演变的理解，并为癌症治疗提供新的治疗靶点。
