Lysophosphatidic Acid Aberrancies and Hepatocellular Carcinoma: Studies in the MDR2 Gene Knockout Mouse

Abstract

Studies show that lysophosphatidic acid (LPA) reprogramming is associated with the development of hepatocellular carcinoma (HCC). This manuscript evaluates the MDR2^−/− model of HCC as a tool to examine the role of LPA reprogramming in the initiation/progression of HCC and identify novel treatment targets. Hepatic tumors developed in MDR2^−/− mice between 9–12 m and serum LPA levels were greater in MDR2^−/− when compared to controls. Blocking LPA biosynthesis/signaling significantly reduced tumor burden. LPA biosynthesis/signaling plays an important role in murine MDR2^−/− model and is potentially linked to regulation of TNFα or other cytokines that are relevant to high-risk patients.

Keywords: :

• HCC
• Multiple Drug Resistance Gene
• TNF Alpha
• cAMP