Sekar, Divya and Dillmann, Christina and Sirait-Fischer, Evelyn and Fink, Annika F. and Zivkovic, Aleksandra and Baum, Natalie and Strack, Elisabeth and Klatt, Stephan and Zukunft, Sven and Wallner, Stefan and Descot, Arnaud and Olesch, Catherine and da Silva, Priscila and von Knethen, Andreas and Schmid, Tobias and Groesch, Sabine and Savai, Rajkumar and Ferreiros, Nerea and Fleming, Ingrid and Ghosh, Sourav and Rothlin, Carla and Stark, Holger and Medyouf, Hind and Bruene, Bernhard and Weigert, Andreas (2022) Phosphatidylserine Synthase PTDSS1 Shapes the Tumor Lipidome to Maintain Tumor-Promoting Inflammation. CANCER RESEARCH, 82 (8). pp. 1617-1632. ISSN 0008-5472, 1538-7445
Full text not available from this repository. (Request a copy)Abstract
An altered lipidome in tumors may affect not only tumor cells themselves but also their microenvironment. In this study, a lipidomics screen reveals increased amounts of phosphatidylser-ine (PS), particularly ether-PS (ePS), in murine mammary tumors compared with normal tissue. PS was produced by phosphatidylserine synthase 1 (PTDSS1), and depletion of Ptdss1 from tumor cells in mice reduced ePS levels accompanied by stunted tumor growth and decreased tumor-associated macrophage (TAM) abundance. Ptdss1-deficient tumor cells exposed less PS during apoptosis, which was recognized by the PS receptor MERTK. Mammary tumors in macrophage-specific Mertk-/- mice showed similarly suppressed growth and reduced TAM infiltration. Transcriptomic profiles of TAMs from Ptdss1-knockdown tumors and Mertk-/- TAMs revealed that macrophage proliferation was reduced when the Ptdss1/Mertk pathway was targeted. Moreover, PTDSS1 expression correlated positively with TAM abundance but negatively with breast carcinoma patient survival. PTDSS1 thus may be a target to modify tumor-promoting inflammation. Significance: This study shows that inhibiting the production of ether-phosphatidylserine by targeting phosphatidylserine syn-thase PTDSS1 limits tumor-associated macrophage expansion and breast tumor growth.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EXPRESSION; CANCER; CELLS; EFFEROCYTOSIS; CLEARANCE; LANDSCAPE; APOPTOSIS; ANALOGS; ORIGIN; MERTK; |
| Subjects: | 100 Philosophy & psychology > 100 Philosophy |
| Divisions: | Philosophy, Art History, History, and Humanities > Institut für Politikwissenschaft > Lehrstuhl für Politische Philosophie und Ideengeschichte - Prof. Dr. Karlfriedrich Herb |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jan 2024 10:06 |
| Last Modified: | 29 Jan 2024 10:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58642 |
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