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Oncotarget. 2016 May 31;7(22):32493-503. doi: 10.18632/oncotarget.8679.

Hepatocyte SLAMF3 reduced specifically the multidrugs resistance protein MRP-1 and increases HCC cells sensitization to anti-cancer drugs.

Author information

1
INSERM-ERi 24 (GRAP) Centre Universitaire de Recherche en Santé CURS, Université de Picardie Jules Verne, Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France.
2
EA 4666 LNPC, Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231) Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France.
3
Department of Microbiology, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, India.
4
Service de Thérapie Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France.
5
Service de Chirurgie Digestive Centre Hospitalier Universitaire Sud, Amiens, France.
6
Service Hépato-Gastroenterologie, Centre Hospitalier Universitaire Sud, Amiens, France.

Abstract

Multidrug resistance MDR proteins (MRPs) are members of the C family of a group of proteins named ATP binding cassette (ABC) transporters. MRPs can transport drugs including anticancer drugs, nucleoside analogs, antimetabolites and tyrosine kinase inhibitors. Drugs used in HCC therapy, such as tyrosine kinase inhibitor sorafenib, are substrates of uptake and/or efflux transporters. Variable expression of MRPs at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. Recently, we reported that the hepatocyte SLAMF3 expression (Signaling Lymphocytic Activation Molecule Family member 3) was reduced in tumor cells from hepatocellular carcinoma (HCC) compared to its high expression in adjacent tissues. In the present study, we make a strong correlation between induced SLAMF3 overexpression and the specific loss of MRP-1 expression and its functionalities as a drugs resistance transporter. No changes were observed on expression of ABCG2 and MDR. More importantly, we highlight a strong inverse correlation between MRP-1 and SLAMF3 expression in patients with HCC. We propose that the SLAMF3 overexpression in cancerous cells could represent a potential therapeutic strategy to improve the drugs sensibility of resistant cells and thus control the therapeutic failure in HCC patients.

KEYWORDS:

HCC; MRP-1; SLAMF3; drugs sensitization; multidrug resistance

PMID:
27081035
PMCID:
PMC5078028
DOI:
10.18632/oncotarget.8679
[Indexed for MEDLINE]
Free PMC Article

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