TGF-β-miR-34a-CCL22 Signaling-induced Treg Cell Recruitment Promotes Venous Metastases of HBV-positive Hepatocellular Carcinoma

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2012 Sep 15

PMID 22975373

Citations 294

Authors

Pengyuan Yang

Qi-Jing Li

Yuxiong Feng

Yun Zhang

Geoffrey J Markowitz

Shanglei Ning

Yuezhen Deng

Jiangsha Zhao

Shan Jiang

Yunfei Yuan

Hong-Yang Wang

Shu-Qun Cheng

Dong Xie

Xiao-Fan Wang

Affiliations

Soon will be listed here.

Abstract

Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for patients with hepatocellular carcinoma (HCC). In this study, we uncovered a causative link between hepatitis B virus (HBV) infection and development of PVTT. Mechanistically, elevated TGF-β activity, associated with the persistent presence of HBV in the liver tissue, suppresses the expression of microRNA-34a, leading to enhanced production of chemokine CCL22, which recruits regulatory T (Treg) cells to facilitate immune escape. These findings strongly suggest that HBV infection and activity of the TGF-β-miR-34a-CCL22 axis serve as potent etiological factors to predispose HCC patients for the development of PVTT, possibly through the creation of an immune-subversive microenvironment to favor colonization of disseminated HCC cells in the portal venous system.

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