TY - JOUR T1 - The HDL particle composition determines its antitumor activity in pancreatic cancer JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101317 VL - 5 IS - 9 SP - e202101317 AU - Raimund Oberle AU - Kristina Kührer AU - Tamina Österreicher AU - Florian Weber AU - Stefanie Steinbauer AU - Florian Udonta AU - Mark Wroblewski AU - Isabel Ben-Batalla AU - Ingrid Hassl AU - Jakob Körbelin AU - Matthias Unseld AU - Matti Jauhiainen AU - Birgit Plochberger AU - Clemens Röhrl AU - Markus Hengstschläger AU - Sonja Loges AU - Herbert Stangl Y1 - 2022/09/01 UR - https://www.life-science-alliance.org/content/5/9/e202101317.abstract N2 - Despite enormous efforts to improve therapeutic options, pancreatic cancer remains a fatal disease and is expected to become the second leading cause of cancer-related deaths in the next decade. Previous research identified lipid metabolic pathways to be highly enriched in pancreatic ductal adenocarcinoma (PDAC) cells. Thereby, cholesterol uptake and synthesis promotes growth advantage to and chemotherapy resistance for PDAC tumor cells. Here, we demonstrate that high-density lipoprotein (HDL)–mediated efficient cholesterol removal from cancer cells results in PDAC cell growth reduction and induction of apoptosis in vitro. This effect is driven by an HDL particle composition–dependent interaction with SR-B1 and ABCA1 on cancer cells. AAV-mediated overexpression of APOA1 and rHDL injections decreased PDAC tumor development in vivo. Interestingly, plasma samples from pancreatic-cancer patients displayed a significantly reduced APOA1-to-SAA1 ratio and a reduced cholesterol efflux capacity compared with healthy donors. We conclude that efficient, HDL-mediated cholesterol depletion represents an interesting strategy to interfere with the aggressive growth characteristics of PDAC. ER -