Lysophosphatidic acid aberrancies and hepatocellular carcinoma: studies in the MDR2 gene knockout mouse.
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.
Department of Surgery, Indiana University, Indianapolis, IN, USA. nskill@iupui.edu
Nicholas
N
Skill
Jianmin
J
Wu
Yan
Y
Xu
Zheng
Z
Zhao
Mary
M
Maluccio
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018432:Drug Resistance, Multiple; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008246:Lysophospholipids / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000097202:ATP-Binding Cassette Sub-Family B Member 4; D000099189:Lysophospholipase D
D018435:ATP Binding Cassette Transporter, Subfamily B; D008246:Lysophospholipids; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids; D010727:Phosphoric Diester Hydrolases; D049349:Receptors, Lysosphingolipid; D000097202:ATP-Binding Cassette Sub-Family B Member 4; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid