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Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8412, Japan
CR-UK Stromal-Tumour Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK
Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8412, Japan
Atopy Research Centre, Juntendo University School of Medicine, Tokyo 113-8412, Japan
Department of Breast Oncology, Juntendo University School of Medicine, Tokyo 113-8412, Japan
* Authors to whom correspondence should be addressed.
Received: 16 January 2013; in revised form: 21 January 2013 / Accepted: 23 January 2013 / Published: 31 January 2013
Abstract: 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.
Keywords: carcinoma-associated fibroblasts (CAFs); tumour microenvironment; stromal-tumour interaction; tumour metastasis; CAF-targeted cancer therapy; innate drug resistance
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MDPI and ACS Style
Togo, S.; Polanska, U.M.; Horimoto, Y.; Orimo, A. Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target. Cancers 2013, 5, 149-169.
Togo S, Polanska UM, Horimoto Y, Orimo A. Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target. Cancers. 2013; 5(1):149-169.
Togo, Shinsaku; Polanska, Urszula M.; Horimoto, Yoshiya; Orimo, Akira. 2013. "Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target." Cancers 5, no. 1: 149-169.