| Autor: |
Andreas Weigert, Bernhard Brüne, Hind Medyouf, Holger Stark, Carla V. Rothlin, Sourav Ghosh, Ingrid Fleming, Nerea Ferreirós, Rajkumar Savai, Sabine Grösch, Tobias Schmid, Andreas von Knethen, Priscila da Silva, Catherine Olesch, Arnaud Descot, Stefan Wallner, Sven Zukunft, Stephan Klatt, Elisabeth Strack, Natalie Baum, Aleksandra Zivkovic, Annika F. Fink, Evelyn Sirait-Fischer, Christina Dillmann, Divya Sekar |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6513600.v1 |
| Popis: |
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 phosphatidylserine (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 synthase PTDSS1 limits tumor-associated macrophage expansion and breast tumor growth. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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