title: The tumor microenvironment in hepatocellular carcinoma (review).
abstract: The tumor microenvironment has been largely studied as a dynamic system             orchestrated by inflammatory cells, including cancer cells, stroma as well as             the extracellular matrix. It is useful to describe and predict the phenotypic             characteristics of cancer. Furthermore, a better understanding of its interplay             with the various aspects of the tumor cells may be utilized for the discovery             of novel molecular targets. Liver cancer is considered a model of the relation             occurring between the tumor micro-environment and tumor development. The chronic             inflammatory status of the liver, sustained by the infection of hepatitis viruses,             as well as the production of cytokines and growth factors within the parenchyma,             lead to an intricate microenvironment. The identification of novel molecular therapeutic             targets may improve the outcome of patients with liver cancer as it remains the             third leading cause of cancer death worldwide. In the present study, the tumor             microenvironment in hepatocellular carcinoma (HCC) was explored by a review of             the literature. Studies on hepatitis virus infections and the consequent chronic             inflammatory status were examined. In this context, immune-mediated and/or virus-related             molecular mechanisms have been hypothesized as being responsible for liver cancer             development. The interlink among HCC microenvironment components, comprising cellular             elements, cytokines, growth factors and several proteins is also described together             with the role of matrix metalloproteinases in HCC development. Finally, the rationale             for targeting tumor-stromal interface is summarized in the context of new therapeutic             opportunities.
authors.affiliation: Laboratory of Translational Oncology and Functional Genomics,                     Section of Pathology and Oncology, University of Catania, Catania, Italy.
authors.forename: Giulia Costanza
authors.initials: GC
authors.lastname: Leonardi
authors.forename: Saverio
authors.initials: S
authors.lastname: Candido
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
authors.forename: Daria
authors.initials: D
authors.lastname: Nicolosi
authors.forename: Fabio
authors.initials: F
authors.lastname: Raiti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Travali
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D030161:Avian Proteins; D016207:Cytokines; C071280:EMF-1 protein, Gallus gallus