- 作者：Yoshifumi Morita ; Takanori Sakaguchi ; Koji Ikegami ; Naoko Goto-Inoue ; Takahiro Hayasaka ; Vu Thi Hang ; Hiroki Tanaka ; Takashi Harada ; Yasushi Shibasaki ; Atsushi Suzuki ; Kazuhiko Fukumoto ; Keisuke Inaba ; Makoto Murakami ; Mitsutoshi Setou ; Hiroyuki Konno
- 关键词：HCC ; hepatocellular carcinoma ; NAFLD ; non-alcoholic fatty liver disease ; IMS ; imaging mass spectrometry ; MALDI ; matrix-assisted laser desorption/ionization ; LPCAT ; lysophosphatidylcholine acyltransferase ; PCA ; principal component analysis ; cPLA2¦Á ; cytoso
- 刊名：Journal of Hepatology
- 出版年：2013
- 出版时间：August, 2013
- 年：2013
- 卷：59
- 期：2
- 页码：292-299
- 全文大小：1363 K
Background & Aims
Several lipid synthesis pathways play important roles in the development and progression of hepatocellular carcinoma (HCC), although the precise molecular mechanisms remain to be elucidated. Here, we show the relationship between HCC progression and alteration of phospholipid composition regulated by lysophosphatidylcholine acyltransferase (LPCAT).Methods
Molecular lipidomic screening was performed by imaging mass spectrometry (IMS) in 37 resected HCC specimens. RT-PCR and Western blotting were carried out to examine the mRNA and protein levels of LPCATs, which catalyze the conversion of lysophosphatidylcholine (LPC) into phosphatidylcholine (PC) and have substrate specificity for some kinds of fatty acids. We examined the effect of LPCAT1 overexpression or knockdown on cell proliferation, migration, and invasion in HCC cell lines.
Results
IMS revealed the increase of PC species with palmitoleic acid or oleic acid at the sn-2-position and the reduction of LPC with palmitic acid at the sn-1-position in HCC tissues. mRNA and protein of LPCAT1, responsible for LPC to PC conversion, were more abundant in HCCs than in the surrounding parenchyma. In cell line experiments, LPCAT1 overexpression enriched PCs observed in IMS and promoted cell proliferation, migration, and invasion. LPCAT1 knockdown did viceversa.
Conclusions
Enrichment or depletion of some specific PCs, was found in HCC by IMS. Alteration of phospholipid composition in HCC would affect tumor character. LPCAT1 modulates phospholipid composition to create favorable conditions to HCC cells. LPCAT1 is a potent target molecule to inhibit HCC progression.