Carcinoma-associated fibroblasts are a promising therapeutic target.
Carcinoma-associated fibroblasts are a promising therapeutic target.
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DOI：
10.3390/cancers5010149
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发表时间：
2013-01-31
期刊：
影响因子：
5.2
通讯作者：
Orimo A
中科院分区：
文献类型：
--
作者：
Togo S;Polanska UM;Horimoto Y;Orimo A
人类癌症经常表现出显着的基质反应，例如所谓的“促纤维增生性基质”或“反应性基质”，其特征是存在大量基质细胞和细胞外基质蛋白。癌相关成纤维细胞（CAF）富含以肌成纤维细胞为代表的活化成纤维细胞群，是肿瘤相关基质中存在的主要细胞类型之一。基质肌成纤维细胞数量的增加通常与人类预后不良的高级别恶性肿瘤有关。 CAF肌成纤维细胞具有通过刺激新血管生成过程以及肿瘤细胞增殖、存活、迁移和侵袭来促进原发性肿瘤发生、生长和进展的能力。此外，已证明 CAF 作为支持远处器官中播散性癌细胞转移定植的生态位。它们对原发性和继发性恶性肿瘤的贡献使这些成纤维细胞成为潜在的治疗靶点，并且它们似乎还与耐药性和肿瘤复发的发展相关。这篇综述总结了我们目前对促肿瘤 CAF 的了解，并讨论了靶向这些细胞以及破坏与肿瘤中其他细胞类型的异型相互作用的治疗可行性，这可能会提高当前抗肿瘤疗法的疗效。
Human carcinomas frequently exhibit significant stromal reactions such as the so-called “desmoplastic stroma” or “reactive stroma”, which is characterised by the existence of large numbers of stromal cells and extracellular matrix proteins. Carcinoma-associated fibroblasts (CAFs), which are rich in activated fibroblast populations exemplified by myofibroblasts, are among the predominant cell types present within the tumour-associated stroma. Increased numbers of stromal myofibroblasts are often associated with high-grade malignancies with poor prognoses in humans. CAF myofibroblasts possess abilities to promote primary tumour development, growth and progression by stimulating the processes of neoangiogenesis as well as tumour cell proliferation, survival, migration and invasion. Moreover, it has been demonstrated that CAFs serve as a niche supporting the metastatic colonisation of disseminated carcinoma cells in distant organs. Their contribution to primary and secondary malignancies makes these fibroblasts a potential therapeutic target and they also appear to be relevant to the development of drug resistance and tumour recurrence. This review summarises our current knowledge of tumour-promoting CAFs and discusses the therapeutic feasibility of targeting these cells as well as disrupting heterotypic interactions with other cell types in tumours that may improve the efficacy of current anti-tumour therapies.