The role of cancer-associated fibroblasts in breast cancer metastasis

Abstract

Breast cancer deaths are primarily caused by metastasis. There are several treatment options that can be used to treat breast cancer. There are, however, a limited number of treatments that can either prevent or inhibit the spread of breast tumor metastases. Thus, novel therapeutic strategies are needed. Studies have increasingly focused on the importance of the tumor microenvironment (TME) in metastasis of breast cancer. As the most abundant cells in the TME, cancer-associated fibroblasts (CAFs) play important roles in cancer pathogenesis. They can remodel the structure of the extracellular matrix (ECM) and engage in crosstalk with cancer cells or other stroma cells by secreting growth factors, cytokines, and chemokines, as well as components of the ECM, which assist the tumor cells to invade through the TME and cause distant metastasis. Clinically, CAFs not only foster the initiation, growth, angiogenesis, invasion, and metastasis of breast cancer but also serve as biomarkers for diagnosis, therapy, and prediction of prognosis. In this review, we summarize the biological characteristics and subtypes of CAFs and their functions in breast cancer metastasis, focusing on their important roles in the diagnosis, prognosis, and treatment of breast cancer. Recent studies suggest that CAFs are vital partners of breast cancer cells that assist metastasis and may represent ideal targets for prevention and treatment of breast cancer metastasis.

Keywords: breast cancer; cancer-associated fibroblasts (CAFs); extracellular matrix (ECM); metastasis; tumor microenvironment (TME).

Figure 1

Breast cancer transfer normal fibroblasts (NFs) to cancer associated fibroblasts (CAFs) through secreting molecules including IL-6, TNF-α, PDGF α/β, OPN, HMGB1 and extracellular vesicles (EVs). Activated CAFs express classic biomarkers like α-SMA, tenascin-C, NG2, S100A4, PDGFR α/β, FAP and podoplanin.

Figure 2

CAFs secret molecules to assist cancer EMT, invasion and metastasis, including chemokines, growth factors, MMPs, EVs and others.