Understanding the Role of Adipocytes and Fibroblasts in Cancer

Abstract

Cancer is currently the second leading cause of death in the United States. There is increasing evidence that the tumor microenvironment (TME) is pivotal for tumorigenesis and metastasis. Recently, adipocytes and cancer-associated fibroblasts (CAFs) in the TME have been shown to play a major role in tumorigenesis of different cancers, specifically melanoma. Animal studies have shown that CAFs and adipocytes within the TME help tumors evade the immune system, for example, by releasing chemokines to blunt the effectiveness of the host defense. Although studies have identified that adipocytes and CAFs play a role in tumorigenesis, adipocyte transition to fibroblast within the TME is fairly unknown. This review intends to elucidate the potential that adipocytes may have to transition to fibroblasts and, as part of the TME, a critical role that CAFs may play in affecting the growth and invasion of tumor cells. Future studies that illuminate the function of adipocytes and CAFs in the TME may pave way for new antitumor therapies.

Figure 1:. The tumor microenvironment (TME).

Tumor cells activate molecular, cellular, and physical changes within host tissue to support tumor growth and progression. The cellular and physical changes help to form the TME. TME includes cancer associated fibroblast (CAFs), immune cells, cancer associated adipocytes (CAAs), a varying degree of stromal cells, blood vessels, and extracellular matrix. CAA: Cancer associated adipocytes, CAFs; Cancer associated fibroblast, TME; Tumor microenvironment

Figure 2:. Crosstalk in the tumor microenvironment (TME).

In crosstalk, tumor cells encounter different cells in the TME, causing morphological changes to cells adjacent to the tumor. Adipocytes within the TME may transition into their activated form, CAAs. Adipocytes may also progressively lose their adipocyte like properties and begin to transition into activated fibroblasts called CAFs. CAFs release cytokines: TGF-β, VEGF, and IL-6. TGF-β down regulates CD-8 T cells. TGF-β and VEGF decrease the antigen presenting ability of the dendritic cells in the TME. IL-6 recruits M2 macrophages to the TME. Release of CXCR4 and CXCR5 may increase melanoma proliferation. CAAs release IL-1β and IL-6, which increase immune evasion of the cancer. CXCR4; chemokine receptor type 4, CXCR5; chemokine receptor type 5, IL-1β; Interleukin beta, IL-6; Interleukin 6, TGF-β; transforming growth factor beta, VEGF; Vascular endothelial growth factor