Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

Cancers

Shinsaku Togo²  Urszula M. Polanska¹  Yoshiya Horimoto³ 

[1] CR-UK Stromal-Tumour Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK;Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8412, Japan;Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8412, Japan

关键词: carcinoma-associated fibroblasts (CAFs);    tumour microenvironment;    stromal-tumour interaction;    tumour metastasis;    CAF-targeted cancer therapy;    innate drug resistance;   

DOI  :  10.3390/cancers5010149

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.