Hierarchical and selective roles of galectins in hepatocarcinogenesis, liver fibrosis and inflammation of hepatocellular carcinoma

Table 3 Galectins in fibrosis-related liver pathologies

Galectin Member	Expression	Function and/or effect	Model	Ref.
Galectin-1	Over-expressed in activated HSCs	Induces proliferation of HSCs via ERK 1/2 through CRD domain	HSCs activated in vitro (cultured on plastic for several days) and in vivo (isolated form rats treated with CCl4 or with bile duct ligation)	[93,94]
	Positive in ICC cells, intracellular expression and secretion	Correlates with histologic dedifferentiation, vascular invasion, and lymph node metastasis	ICC tissue samples, CCKS1 cholangiocarcinoma cell line	[96]
Galectin-3	Over-expressed in activated HSCs	Induces proliferation via ERK 1/2 involving PKA and PKC pathwaysDependent on CRD domain	HSCs activated in vitro (cultured on plastic for several days) and in vivo (isolated form rats treated with bile duct ligation)	[94]
		Intracellular Gal3 is required for activation of HSCs via TGF-β	HSCs activated in vivo (isolated form rats treated with CCl4)	[132]
		Extracellular Gal3 required for activation of HSCs. Integrin and CRD dependent effect	HSCs activated in vivo (isolated from rats with bile duct ligation)	[134]
		NFκβ induces expression and secretion of Gal3 in activated HSCs
	Up-regulated in injured/cirrhotic hepatocytes	Poor liver function	Human fibrotic liver samples and extracts from rats treated with CCl4	[124,133,136]
		Related to the preneoplastic and early neoplastic stages of ICC	ICC tissue samples	[96,137]
	Positive in ICC cells	Intracellular expression is associated withanti-apoptotic activity and resistance to chemotherapeutic agents	ICC cell lines	[138]

HSC: Hepatic stellate cells; CRD: Carbohydrate recognition domain; ERK: Extracellular signal-regulated kinase; ICC: Intrahepatic cholangiocarcinoma; PKA: Protein kinase A; PKC: Protein kinase C.