Cancer-Associated Fibroblasts: The Origin, Biological Characteristics and Role in Cancer-A Glance on Colorectal Cancer

Abstract

The therapeutic approaches to cancer remain a considerable target for all scientists around the world. Although new cancer treatments are an everyday phenomenon, cancer still remains one of the leading mortality causes. Colorectal cancer (CRC) remains in this category, although patients with CRC may have better survival compared with other malignancies. Not only the tumor but also its environment, what we call the tumor microenvironment (TME), seem to contribute to cancer progression and resistance to therapy. TME consists of different molecules and cells. Cancer-associated fibroblasts are a major component. They arise from normal fibroblasts and other normal cells through various pathways. Their role seems to contribute to cancer promotion, participating in tumorigenesis, proliferation, growth, invasion, metastasis and resistance to treatment. Different markers, such as a-SMA, FAP, PDGFR-β, periostin, have been used for the detection of cancer-associated fibroblasts (CAFs). Their detection is important for two main reasons; research has shown that their existence is correlated with prognosis, and they are already under evaluation as a possible target for treatment. However, extensive research is warranted.

Keywords: CAFs; cancer-associated fibroblasts; colorectal cancer; tumor microenvironment.

Figure 1

Origin of CAFs and their relation to cancer. CAFs might be derived from mesenchymal cells, fibroblasts, epithelial cells, endothelial cells, adipocytes, pericytes and smooth muscle cells. The main markers that can be recognized regarding GI cancers are: FAP, α-SMA, vimentin, FSP1, PDFGR-α/β and periostin. They are related to cancer by promoting tumor growth, cancer cell proliferation, invasion and metastasis, angiogenesis and immune remodeling.