title: Lipoprotein lipase links dietary fat to solid tumor cell proliferation.
abstract: Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain preformed, diet-derived FA by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further show that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or FA uptake will be necessary to target the requirement of cancer cells for FA.
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kuemmerle
authors.forename: Evelien
authors.initials: E
authors.lastname: Rysman
authors.forename: Portia S
authors.initials: PS
authors.lastname: Lombardo
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Flanagan
authors.forename: Brea C
authors.initials: BC
authors.lastname: Lipe
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Wells
authors.forename: Jason R
authors.initials: JR
authors.lastname: Pettus
authors.forename: Heather M
authors.initials: HM
authors.lastname: Froehlich
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Memoli
authors.forename: Peter M
authors.initials: PM
authors.lastname: Morganelli
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
authors.forename: Luika A
authors.initials: LA
authors.lastname: Timmerman
authors.forename: Leila
authors.initials: L
authors.lastname: Chaychi
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Fricano
authors.forename: Burton L
authors.initials: BL
authors.lastname: Eisenberg
authors.forename: William B
authors.initials: WB
authors.lastname: Coleman
authors.forename: William B
authors.initials: WB
authors.lastname: Kinlaw
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004041:Dietary Fats / Q000378:metabolism*; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D018955:CD36 Antigens; D004041:Dietary Fats; D054872:Fatty Acid Synthesis Inhibitors; D005227:Fatty Acids; D034741:RNA, Small Interfering; D008071:Lipoprotein Lipase