Chemokines and their receptors play important roles in the development of hepatocellular carcinoma

Table 2 Pleiotropic functions of chemokines in hepatocellular carcinoma

Categories	Chemokines	Chemokine origins	Receptors participated	Functions
Inflammation	CXCL8	HCC cells	Not clarified	Increasing inflammatory cytokines
	CXCL16	HCC cells	CXCR6	(IL-6, IL-8, etc.) and recruiting leukocytes
	CCL3	HCC cells and HSC	CCR3	(macrophages, neutrophils, etc.)
	CCL5	HCC cells and HSC	CCR5
Influences on immune cells	CXCL5	HCC cells	Not clarified	Chemotaxis of neutrophils
	CXCL9	HCC cells and endothelial cells	CXCR3	Chemotaxis of T cells
	CXCL10	HCC cells, macrophages and TILs	CXCR3	Chemotaxis of T cells and NK cells
	CXCL16	HCC cells	CXCR6	Chemotaxis of neutrophils
	CCL2	HCC cells, macrophages and TILs	CCR2	Chemotaxis of HSC, macrophages, MDSC, and T cells
	CCL5	HCC cells, macrophages and TILs	CCR5	Chemotaxis of T cells and NK cells
	CCL20	HCC cells	CCR6	Chemotaxis of Th17 cells and Tregs
	CCL22	HCC cells and DCs	CCR4	Chemotaxis of Tregs
Angiogenesis	CXCL3, CXCL5	HCC cells	Not clarified	Promoting angiogenesis via mechanisms not clarified
	CXCL8	CSCs	Not clarified	Promoting endothelial cell tube formation
	CXCL9	Not clarified	CXCR3	Inhibiting angiogenesis by abrogation of VEGF effects
	CXCL12	Endothelia cells	CXCR4, CXCR7	Enhancing angiogenesis through VEGF
	CXCL16	HCC cells	CXCR6	Promoting angiogenesis via mechanisms not clarified
	CCL2	HCC cells and endothelial cells	CCR2	Enhancing the proliferation of endothelial cells
	CCL3	HCC cells and endothelial cells	CCR1, CCR5	Enhancing the proliferation of endothelial cells
Direct effects on HCC cells	CXCL1, CXCL2, CXCL16	Not clarified	Not clarified	Enhancing the growth of HCC cells
	CXCL5	HCC cells	Not clarified	Enhancing the migration, invasion, and growth of HCC cells
	CXCL8	Not clarified	CXCR2	Enhancing the migration of HCC cells
	CXCL10	hepatocytes	Not clarified	Enhancing the survival of hepatocytes
	CXCL12	HCC cells, HSC	CXCR4, CXCR7	Enhancing the migration, invasion, growth and survival of HCC cells
	CCL2	WAT, CAF	CCR2	Enhancing the migration, invasion, and growth of HCC cells
	CCL3, CCL5	Not clarified	CCR1	Enhancing the migration and invasion of HCC cells
	CCL15	HCC cells	Not clarified
	CCL20	HCC cells	CCR6	Enhancing the migration, invasion, and growth of HCC cells

HSC: Hepatic stellate cells; TILs: Tumor-infiltrating leucocytes; MDSC: Myeloid derived suppressor cells; Tregs: Regulatory T cells; DCs: Dendritic cells; VEGF: Vascular endothelial growth factor; CSCs: Cancer stem cells; WAT: White adipose tissue; CAF: Cancer-associated fibroblast; HCC: Hepatocellular carcinoma.