TY  - JOUR
A1  - Gruden, Eva
A1  - Kienzl, Melanie
A1  - Hasenoehrl, Carina
A1  - Sarsembayeva, Arailym
A1  - Ristic, Dusica
A1  - Theresa Schmid, Sophie
A1  - Maitz, Kathrin
A1  - Taschler, Ulrike
A1  - Hahnefeld, Lisa Katharina
A1  - Gurke, Robert
A1  - Thomas, Dominique Jeanette
A1  - Kargl, Julia
A1  - Schicho, Rudolf
T1  - Tumor microenvironment-derived monoacylglycerol lipase provokes tumor-specific immune responses and lipid profiles
T2  - Prostaglandins, Leukotrienes and Essential Fatty Acids
N2  - 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 (KrasLSL-G12D/p53fl/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.
KW  - Monoacylglycerol lipase
KW  - Tumor microenvironment
KW  - Endocannabinoids
KW  - (lyso)phospholipids
KW  - Melanoma
KW  - Non-small cell lung cancer
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77107
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-771078
SN  - 0952-3278
VL  - 196
IS  - 102585
PB  - Elsevier
CY  - Amsterdam
ER  -