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Review
. 2015 Dec 11;7(4):2443-58.
doi: 10.3390/cancers7040902.

Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

Kazuyoshi Shiga  1 , Masayasu Hara  2 , Takaya Nagasaki  3 , Takafumi Sato  4 , Hiroki Takahashi  5 , Hiromitsu Takeyama  6
Affiliations
Review

Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

Kazuyoshi Shiga et al. Cancers (Basel). .

Abstract

Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy.

Keywords: angiogenesis; cancer-associated fibroblasts; drug resistance; interleukin 6; origin; tumor-stroma interaction.

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Figures

Figure 1
Figure 1
Origins of cancer-associated fibroblasts (CAFs): CAFs are considered to originate from various cells such as resident fibroblasts, adipocytes, epithelial cells (through epithelial mesenchymal transition: EMT), endothelial cells (through endothelial mesenchymal transition: endMT), bone marrow derived mesenchymal stem cells, and hematopoietic stem cells.
Figure 2
Figure 2
Tumor-stroma interactions and the role of CAFs. CAFs contribute to cancer proliferation, invasion, metastasis, and angiogenesis through several factors.
Figure 3
Figure 3
Angiogenesis and CAFs. CAFs produce IL-6. VEGF that is induced by IL-6 and several other factors (FGF, PDGF, and SDF-1) promotes angiogenesis.
See this image and copyright information in PMC

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