Fig. 1
From: Drug delivery strategy in hepatocellular carcinoma therapy
The tumor microenvironment of HCC. CAFs are activated by PDGF, IL-6, and IL-1α, which are secreted by HCC. Activated CAFs produce EGF, HGF and FGF to promote rapid proliferation; IL-8, COX-2 and SPARC to aggregate and stimulate macrophage production; MMP to degrade the ECM; chemokine to recruit T cells and maintain the protumorigenic inflammatory environment. HSCs are activated by liver inflammation, and generate cytokines, chemokines, growth factors, and ECM as well as induce the formation of tumor blood vessels and lymphatics to promote tumor growth. M1 macrophages are activated by interferon-γ, while M2 macrophages are activated by IL-4, IL-10, and IL-13. M2 macrophages produce VEGF and EGF to promote angiogenesis, growth and the invasion of tumors. Components of ECM, including collagen, elastin, hyaluronic acid, proteoglycan, polysaccharide, related enzymes, growth factors and etc., play an important role in regulating cell proliferation, promoting microenvironmental fibrosis and angiogenesis. Dysregulation of the ECM leads to cell transformation and metastasis