Transforming growth factor β (TGF-β) and inflammation in cancer

Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
Cytokine & growth factor reviews (Impact Factor: 5.36). 12/2009; 21(1):49-59. DOI: 10.1016/j.cytogfr.2009.11.008
Source: PubMed


The transforming growth factor beta (TGF-beta) has been studied with regard to the regulation of cell behavior for over three decades. A large body of research has been devoted to the regulation of epithelial cell and derivative carcinoma cell populations in vitro and in vivo. TGF-beta has been shown to inhibit epithelial cell cycle progression and promote apoptosis that together significantly contribute to the tumor suppressive role for TGF-beta during carcinoma initiation and progression. TGF-beta is also able to promote an epithelial to mesenchymal transition that has been associated with increased tumor cell motility, invasion and metastasis. However, it has now been shown that loss of carcinoma cell responsiveness to TGF-beta stimulation can also promote metastasis. Interestingly, enhanced metastasis in the absence of a carcinoma cell response to TGF-beta stimulation has been shown to involve increased chemokine production resulting in recruitment of pro-metastatic myeloid derived suppressor cell (MDSC) populations to the tumor microenvironment at the leading invasive edge. When present, MDSCs enhance angiogenesis, promote immune tolerance and provide matrix degrading enzymes that promote tumor progression and metastasis. Further, the recruitment of MDSC populations in this context likely enhances the classic role for TGF-beta in immune suppression since the MDSCs are an abundant source of TGF-beta production. Importantly, it is now clear that carcinoma-immune cell cross-talk initiated by TGF-beta signaling within the carcinoma cell is a significant determinant worth consideration when designing therapeutic strategies to manage tumor progression and metastasis.

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Available from: Brian Bierie, Jan 16, 2015
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    • "The ectonucleotidases-degraded ATP led to adenosine release and, subsequently, suppression of helper CD4 + and cytotoxic CD8 + T cell effector functions. TGFí µí»½ which is commonly found in tumour microenvironments has, therefore , been suggested to augment the immune suppressive and tumour-promoting functions of Th17 cells [75] [76]. Th17 cells have also been reported to promote cancer by virtue of their ability to induce angiogenesis [65]. "
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    • "In addition, tumor cells create an immunosuppressive microenvironment via the elaboration of various cytokines and chemokines, such as TGF-β, IL- 10, prostaglandins (PGs), chemokine (C-C motif) ligand 2 (CCL-2), and VEGF. TGF-β inhibits T-and natural killer (NK)-cell proliferation and function [14] and promotes the expansion of regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs) [15] [16] . IL-10 inhibits antitumor immunity [17] . "
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    • "The low numbers of CD4+CD103+-lymphocytes in RE might indicate low levels of tissue TGF-β, which led to a diminished ability of CD4+-cells to upregulate CD103 or to an impaired influx of CD4+CD103+-cells from peripheral blood. Lower levels of TGF-β can point at a pro-inflammatory environment [42]. This is supported by the finding that CD103+-lymphocytes have an immunosuppressive phenotype placing them in an anti-inflammatory tissue environment [27], [43], [44]. "
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