Next Article in Journal
Mouse Genetic Models Reveal Surprising Functions of IkB Kinase Alpha in Skin Development and Skin Carcinogenesis
Previous Article in Journal
Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials
Cancers 2013, 5(1), 149-169; doi:10.3390/cancers5010149
Review

Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

1,* , 2, 3,4,5 and 2,3,4,*
1 Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8412, Japan 2 CR-UK Stromal-Tumour Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK 3 Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8412, Japan 4 Atopy Research Centre, Juntendo University School of Medicine, Tokyo 113-8412, Japan 5 Department of Breast Oncology, Juntendo University School of Medicine, Tokyo 113-8412, Japan
* Authors to whom correspondence should be addressed.
Received: 16 January 2013 / Revised: 21 January 2013 / Accepted: 23 January 2013 / Published: 31 January 2013
View Full-Text   |   Download PDF [389 KB, uploaded 31 January 2013]   |   Browse Figure

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 carcinoma-associated fibroblasts (CAFs); tumour microenvironment; stromal-tumour interaction; tumour metastasis; CAF-targeted cancer therapy; innate drug resistance
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


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.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert