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World J Gastroenterol. Apr 21, 2014; 20(15): 4128-4140
Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4128
Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma
Bhavna Rani, Yuan Cao, Andrea Malfettone, Ciprian Tomuleasa, Isabel Fabregat, Gianluigi Giannelli
Bhavna Rani, Yuan Cao, Gianluigi Giannelli, Department of Medical Biosciences and Human Oncology, Padiglione Semeiotica Medica, 70124 Bari, Italy
Andrea Malfettone, Isabel Fabregat, Bellvitge Biomedical Research Institute (IDIBELL), 08028 Barcelona, Spain
Isabel Fabregat, Department of Physiological Sciences II, University of Barcelona, 08028 Barcelona, Spain
Ciprian Tomuleasa, Department of Hematology, Center for Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj Napoca, Romania
Author contributions: Rani B, Cao Y, Malfettone A and Tomuleasa C reviewed the literature; Fabregat I contributed to the work; Giannelli G organized the manuscript.
Supported by EU-Marie Curie Initial Training Network (ITN), FP7-PEOPLE-2012-ITN 2012, Grant Agreement No. 316549
Correspondence to: Gianluigi Giannelli, MD, Department of Medical Biosciences and Human Oncology, Padiglione Semeiotica Medica, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy. gianluigi.giannelli@uniba.it
Telephone: +39-080-5478233 Fax: +39-080-5478234
Received: October 6, 2013
Revised: January 11, 2014
Accepted: February 16, 2014
Published online: April 21, 2014
Processing time: 193 Days and 12.6 Hours
Abstract

Hepatocellular carcinoma is difficult to treat, primarily because the underlying molecular mechanisms driving clinical outcome are still poorly understood. Growing evidence suggests that the tissue microenvironment has a role in the biological behavior of the tumor. The main clinical issue is to identify the best target for therapeutic approaches. Here, we discuss the hypothesis that the entire tissue microenvironment might be considered as a biological target. However, the tissue microenvironment consists of several cellular and biochemical components, each of which displays a distinct biological activity. We discuss the major components of this environment and consider how they may interact to promote tumor/host crosstalk.

Keywords: Tissue microenvironment; Hepatocellular carcinoma; Transforming growth factor-beta; Laminin-5; Cancer stem cells; Therapy; Target therapy

Core tip: We discuss a new hypothesis for therapeutic approaches in hepatocellular carcinoma (HCC). This novel idea is to regard the entire liver as responsible for the onset, growth and progression of HCC. In this scenario, we focus on the tissue microenvironment components as an ideal target for systemic therapies, taking into account the tumor/host interactions.