Schicho R

References (2)

Title : Tumor microenvironment-derived monoacylglycerol lipase provokes tumor-specific immune responses and lipid profiles - Gruden_2023_Prostaglandins.Leukot.Essent.Fatty.Acids_196_102585
Author(s) : Gruden E , Kienzl M , Hasenoehrl C , Sarsembayeva A , Ristic D , Schmid ST , Maitz K , Taschler U , Hahnefeld L , Gurke R , Thomas D , Kargl J , Schicho R
Ref : Prostaglandins Leukot Essent Fatty Acids , 196 :102585 , 2023
Abstract : We recently described that monoacylglycerol lipase (MGL) is present in the tumor microenvironment (TME), increasing tumor growth. In this study we compare the implications of MGL deficiency in the TME in different tumor types. We show that subcutaneous injection of KP (Kras(LSL-G12D)/p53(fl/fl), mouse lung adenocarcinoma) or B16-F10 cells (mouse melanoma) induced tumor growth in MGL wild type (WT) and knockout (KO) mice. MGL deficiency in the TME attenuated the growth of KP cell tumors whereas tumors from B16-F10 cells increased in size. Opposite immune cell profiles were detected between the two tumor types in MGL KO mice. In line with their anti-tumorigenic function, the number of CD8(+) effector T cells and eosinophils increased in KP cell tumors of MGL KO vs. WT mice whereas their presence was reduced in B16-F10 cell tumors of MGL KO mice. Differences were seen in lipid profiles between the investigated tumor types. 2-arachidonoylglycerol (2-AG) content significantly increased in KP, but not B16-F10 cell tumors of MGL KO vs. WT mice while other endocannabinoid-related lipids remained unchanged. However, profiles of phospho- and lysophospholipids, sphingomyelins and fatty acids in KP cell tumors were clearly distinct to those measured in B16-F10 cell tumors. Our data indicate that TME-localized MGL impacts tumor growth, as well as levels of 2-AG and other lipids in a tumor specific manner.
ESTHER : Gruden_2023_Prostaglandins.Leukot.Essent.Fatty.Acids_196_102585
PubMedSearch : Gruden_2023_Prostaglandins.Leukot.Essent.Fatty.Acids_196_102585
PubMedID: 37573716

Title : Carboxylesterase 2 proteins are efficient diglyceride and monoglyceride lipases possibly implicated in metabolic disease - Chalhoub_2021_J.Lipid.Res__100075
Author(s) : Chalhoub G , Kolleritsch S , Maresch LK , Taschler U , Pajed L , Tilp A , Natmessnig H , Rosina P , Kien B , Radner FPW , Schicho R , Oberer M , Schoiswohl G , Haemmerle G
Ref : J Lipid Res , :100075 , 2021
Abstract : Carboxylesterase 2 (CES2/Ces2) proteins exert established roles in (pro)drug metabolism. Recently, human and murine CES2/Ces2c have been discovered as triglyceride (TG) hydrolases implicated in the development of obesity and fatty liver disease. The murine Ces2 family consists of seven homologous genes as opposed to a single CES2 gene in humans. However, the mechanistic role of Ces2 protein family members is not completely understood. In this study, we examined activities of all Ces2 members towards TGs, diglycerides (DGs) and monoglycerides (MGs) as substrate. Besides CES2/Ces2c, we measured significant TG hydrolytic activities for Ces2a, Ces2b, and Ces2e. Notably, these Ces2 members and CES2 efficiently hydrolyzed DGs and MGs and their activities even surpassed those measured for TG hydrolysis. The localization of CES2/Ces2c proteins at the ER may implicate a role of these lipases in lipid signaling pathways. We found divergent expression of Ces2 genes in the liver and intestine of mice on high fat diet, which could relate to changes in lipid signaling. Finally, we demonstrate reduced CES2 expression in the colon of patients with inflammatory bowel disease and a similar decline in Ces2 expression in the colon of a murine colitis model. Together, these results demonstrate that CES2/Ces2 members are highly efficient DG and MG hydrolases that may play an important role in liver and gut lipid signaling.
ESTHER : Chalhoub_2021_J.Lipid.Res__100075
PubMedSearch : Chalhoub_2021_J.Lipid.Res__100075
PubMedID: 33872605
Gene_locus related to this paper: human-CES2 , mouse-Ces2a , mouse-Ces2b , mouse-Ces2c