Release Time:2019-03-13  Hits:

Indexed by: Journal Article

Date of Publication: 2016-05-01

Journal: BIOMEDICINE & PHARMACOTHERAPY

Included Journals: Scopus、PubMed、SCIE

Volume: 80

Page Number: 289-297

ISSN: 0753-3322

Key Words: Tumor immunesurveillance; Hepatocellular carcinoma; CD147; Cyclophilin A; Chemotaxis

Abstract: T cells play an important role in tumor immune surveillance. CD147 is a member of immunoglobulin superfamily present on the surface of many tumor cells and mediates malignant cell behaviors. Cyclophilin A (CypA) is an intracellular protein promoting inflammation when released from cells. CypA is a natural ligand for CD147. In this study, CD147 specific short hairpin RNAs (shRNA) were transfected into murine hepatocellular carcinoma Hepa1-6 cells to assess the effects of CD147 on hepatoma cells escaping from immune surveillance of T cells. We found extracellular CypA stimulated cell proliferation through CD147 by activating ERK1/2 signaling pathway. Downregulation of CD147 expression on Hepa16 cells significantly suppressed tumor progression in vivo, and decreased cell viability when co-cultured with T cells in vitro. Importantly, knockdown of CD147 on Hepa1-6 cells resulted in significantly increased T cells chemotaxis induced by CypA both in vivo and in vitro. These findings provide novel mechanisms how tumor cells escaping from immune surveillance of T cells. We provide a potential therapy for hepatocellular carcinoma by targeting CD147 or CD147-CypA interactions. (C) 2016 Elsevier Masson SAS. All rights reserved.