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.
Highlights
Tumours are a complex tissue composed of carcinoma cells, various types of stromal cells and dense extracellular matrix (ECM)
Our study showed that subcutaneous co-implantation of human mammary stromal fibroblasts with breast carcinoma cells into recipient mice resulted in transdifferentiation of these fibroblasts into tumour-promoting Carcinoma-associated fibroblasts (CAFs) myofibroblasts during tumour progression [38]
Stromal POSTN was shown to interact with Wnt ligands to augment the presumed signalling activity. These findings demonstrated that CAF-produced POSTN in the lung drives metastatic colonisation of disseminated breast carcinoma cells via induction of Wnt signalling and the cancer stem cell (CSC) trait
Summary
Tumours are a complex tissue composed of carcinoma cells, various types of stromal cells and dense extracellular matrix (ECM). The identification of cellular and molecular targets abrogating stromal-tumour cell interactions and attenuating tumourigenesis is currently one of the most important subjects in translational oncology. Achieving this goal is essential for increasing the efficacy of conventional therapies in combination with the stroma-based therapeutic approaches [12,13]. Considerable numbers of CAFs are frequently observed within the tumour-associated stroma of various human cancers, including those of the breast, prostate, lung, colon and pancreas [14,15] These cells contain distinct subpopulations of activated fibroblasts exemplified by myofibroblasts positive for. We highlight the biological significance of tumour-promoting functions of CAFs and discuss their potential therapeutic applications
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