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http://crossmark.crossref.org/dialog/?doi=10.1007/s00441-016-2467-x&domain=pdf
Web End = Cell Tissue Res (2016) 365:607619
DOI 10.1007/s00441-016-2467-x
http://crossmark.crossref.org/dialog/?doi=10.1007/s00441-016-2467-x&domain=pdf
Web End = REVIEW
Fibroblast activation in cancer: when seed fertilizes soil
Sanya-Eduarda Kuzet1 & Cedric Gaggioli1
Received: 21 April 2016 /Accepted: 1 July 2016 /Published online: 29 July 2016 # Springer-Verlag Berlin Heidelberg 2016
Abstract In solid cancers, activated fibroblasts acquire the capacity to provide fertile soil for tumor progression. Specifically, cancer-associated fibroblasts (CAFs) establish a strong relationship with cancer cells. This provides advantages to both cell types: whereas cancer cells initiate and sustain CAF activation, CAFs support cancer cell growth, motility and invasion. This results in tumor progression, metastasis and chemoresistance. Numerous studies have detailed the mechanisms involved in fibroblast activation and cancer progression, some of which are reviewed in this article. Cancer cells and CAFs are Bpartners in crime^, and their interaction is supported by inflammation. An understanding of the enemy, the cancer cell population and its Ballies^ should provide novel opportunities for targeted-drug development.
Keywords Carcinoma-associated fibroblasts . Tumor microenvironment . Inflammation . Cancer
Introduction
Tumor development and progression is not only dependent on the malignancy of cancer cells (Kalluri 2003). Like their normal counterparts, cancer epithelial cells are supported by a complex microenvironment that is mainly composed of extracellular matrix (ECM), immune cells, blood vessels, cytokines, growth factors and importantly, non-epithelial cells such as fibroblasts (Liotta and Kohn 2001). Fibroblasts constitute the most abundant population within the family of connective-tissue cells. The physiological role of fibroblasts includes the synthesis of ECM components, notably collagens, the regulation of tissue homeostasis and inflammation and the differentiation of the surrounding cells (Tomasek et al. 2002). Furthermore, fibro-blasts are responsible for the production of the matrix metalloproteinases (MMPs; Simian et al. 2001) that are involved in matrix remodeling, cell proliferation, motility and death, further underscoring the role of fibroblasts in the maintenance of ECM homeostasis. The ability of fibroblasts to secrete diverse growth factors is another essential function that facilitates interactions between mesenchymal and epithelial cells (Wiseman and Werb 2002). Proper communication between cells is essential for the physiological growth and differentiation of mesenchymal tissue and relies not only on cell-to-cell interactions but also on cell-ECM interactions. In addition, fibroblasts are star players in the wound healing processes (Shaw and Martin 2009)....