Inflammatory fibroblasts in cancer

Abstract

The association between inflammation and cancer has been studied widely. Indeed, the tumor microenvironment is influenced by inflammatory cells and affects tumor progression, tumor growth, and the survival of cancer cells. Also, the tumor microenvironment is essential to invasion and metastasis of cancer. Fibroblasts, immune cells, the extracellular matrix and other various components all constitute the tumor stroma, ordinarily referred to as the 'reactive stroma'. Cancer-associated fibroblasts (CAFs), which are activated fibroblasts and one of the components of the tumor microenvironment, are associated with cancer progression, invasiveness and metastasis, and their functional contributions to these processes are beginning to emerge. CAFs mediate tumor-promoting inflammation through various signaling pathways. Epithelial-mesenchymal transition is a process for producing mesenchymal cells during invasion and metastasis of cancer cells. Fibroblasts have been identified as a key player in this mechanism. In the present review, we summarize the relationships between fibroblasts, inflammatory response, the tumor microenvironment and cancer progression. This review provides useful information for the development of cancer prevention and treatment therapies through controlling the inflammatory responses.

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

“…Consistently, we have observed an increase in mRNAs for IL‐8 suggesting that both, IL‐8 and SDF‐1 could contribute to phenotypic changes observed in myofibroblasts cocultured with H. pylori . SDF‐1 and IL‐8 can synergistically increase endothelial cell proliferation and migration, boosting the angiogenic pathway with IL‐8, predominantly induced in gastric cancer 35, 38, 64. The secretion of IL‐6, FAP, and IL‐8 by CAFs plays pivotal role in macrophage differentiation or M2 polarization resulting in an immunosuppressive microenvironment 36…”

“…SDF-1 and IL-8 can synergistically increase endothelial cell proliferation and migration, boosting the angiogenic pathway with IL-8, predominantly induced in gastric cancer. 35,38,64 The secretion of IL-6, FAP, and IL-8…”

“…[32][33][34] The proinflammatory factors released by CAFs, such as IL-6, COX-2 and CXCL1, FSP1, CXCL9, CXCL10 (IP-10), and CXCL12 (SDF-1 stromal cell-derived factor 1), were implicated in the mechanism of tumor growth and neoplastic cell invasion. [35][36][37][38][39] The CAFs secrete proangiogenic factors, such as IL-8, SDF-1, vascular endothelial factor (VEGF), and fibroblast growth factor (FGF), into an environment of other stromal cells including endothelial cells to promote tumor angiogenesis. 30,35,38,39 CAFs may enhance invasion of the cancer cells through expression of TGF β, potent EMT inducer, and HGF, which has been shown to promote breast tumorigenesis.…”

“…[35][36][37][38][39] The CAFs secrete proangiogenic factors, such as IL-8, SDF-1, vascular endothelial factor (VEGF), and fibroblast growth factor (FGF), into an environment of other stromal cells including endothelial cells to promote tumor angiogenesis. 30,35,38,39 CAFs may enhance invasion of the cancer cells through expression of TGF β, potent EMT inducer, and HGF, which has been shown to promote breast tumorigenesis. 39,40 Since fibroblasts may…”

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

“…CAFs are crucial in the initiation, growth, and migration properties of gastric cancer cells [235,236]. They are responsible for the release of carcinogenic and proinflammatory factors including interleukin-6 (Il-6), cyclooxygenase-2 (COX-2), chemokine (C-X-C motif) ligand 1 (Cxcl1), chemokine (C-X-C motif) ligand 9 (Cxcl9), interferon gamma-induced protein 10 (Cxcl10), stromal cell-derived factor 1 (Cxcl12), and fibroblast-specific protein 1 (FSP1), which promote the EMT process and induce carcinogenesis, promoting migration and invasion [237][238][239]. Activation of death receptor 4 (TRAIL receptor 1, TRAILR1) and ensuing activation of caspase 8 by CAFs induce apoptosis in gastric cells [240,241].…”