Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8412, Japan.
Cancers (Basel). 2013 Jan 31;5(1):149-69. doi: 10.3390/cancers5010149.
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.
人类癌经常表现出显著的基质反应，如所谓的“纤维母细胞性间质”或“反应性间质”，其特征在于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）富含激活的成纤维细胞群体，例如肌成纤维细胞，是肿瘤相关基质中主要存在的细胞类型之一。基质中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 肌成纤维细胞通过刺激新血管生成以及肿瘤细胞增殖、存活、迁移和侵袭过程，具有促进原发性肿瘤发展、生长和进展的能力。此外，已经证明 CAF 作为支持播散性癌细胞在远处器官转移定植的小生境。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，并且它们似乎与药物耐药性和肿瘤复发的发展有关。这篇综述总结了我们目前对促进肿瘤的 CAF 的认识，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质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。
