title: Role of chemokine pathways in hepatobiliary cancer.
abstract: Persistent hepatic inflammation resulting from hepatitis B or C virus infections (HBV or HCV, respectively), obesity-associated non-alcoholic steatohepatitis (NASH) or alcohol abuse is a hallmark feature of chronic liver diseases and appears to be an essential prerequisite of hepatocarcinogenesis. The inflammatory processes in the liver are regulated by various chemokines, which orchestrate the interaction between parenchymal liver cells, Kupffer cells (resident macrophages), hepatic stellate cells (HSC), endothelial cells, and infiltrating immune cells. In consequence, these cellular interactions result in the re-modeling of the hepatic microenvironment toward a pro-inflammatory, pro-fibrotic, pro-angiogenic and thus pre-neoplastic milieu. Once developed, liver neoplasms provoke pro- and anti-tumor immune responses that are also critically regulated through differential activation of chemokine pathways. With respect to hepatobiliary cancers, including hepatocellular carcinoma (HCC), gallbladder cancer and cholangiocellular carcinoma (cholangiocarcinoma), together belonging to the highest causes of cancer-related deaths worldwide, this review article will give an overview of chemokine pathways involved in both the establishment of a pro-tumorigenic microenvironment as well as the development and progression of hepatobiliary cancer. Pharmaceutical targeting of chemokine pathways is a promising approach to treat or even prevent hepatobiliary cancer.
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH University, Aachen, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Ehling
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH University, Aachen, Germany. Electronic address: frank.tacke@gmx.net.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D018925:Chemokines
keywords: Angiogenesis; CCL2; CCR2; CXCL12; CXCR4; Macrophages