title: Tumor Microenvironment, a Paradigm in Hepatocellular Carcinoma Progression and Therapy.
abstract: Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. Different etiological factors such as hepatitis B and C virus, alcohol and diabetes cause liver injury followed by inflammation, necrosis and hepatocytes proliferation. Continuous cycles of this destructive-regenerative process culminates in liver cirrhosis which is characterized by regenerating nodules that progress to dysplastic nodules and ultimately HCC. Despite its significance, there is only an elemental understanding of the pathogenetic mechanisms, and there are only limited therapeutic options. Therefore, the study of the involved molecular mechanisms can open a new insight to define more effective treatment strategies. A variety of alterations have been reported in HCC patients, particularly the cancer-associated microenvironment components including immune cells, fibroblast cells, endothelial cells and extracellular matrix can support the neoplastic cells to proliferate, growth and invade. This review summarizes the current state of knowledge and highlights the principal challenges that are relevant to controlling this milieu.
authors.affiliation: Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 63461, Iran. maryam_tahmaseby@yahoo.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Tahmasebi Birgani
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, Florence 50134, Italy. vinicio.carloni@unifi.it.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Carloni
mesh_terms: D000818:Animals; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D002450:Cell Communication; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055166:Hepatic Stellate Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D015415:Biomarkers
keywords: cancer therapy; endothelial cells; extracellular matrix; fibroblast cells; hepatocellular carcinoma; immune cells; tumor microenvironment