Title: Lipoprotein lipase links dietary fat to solid tumor cell proliferation
Authors: Kuemmerle, Nancy B ×
Rysman, Evelien
Lombardo, Portia S
Flanagan, Alison J
Lipe, Brea C
Wells, Wendy A
Pettus, Jason R
Froehlich, Heather M
Memoli, Vincent A
Morganelli, Peter M
Swinnen, Johan
Timmerman, Luika A
Chaychi, Leila
Fricano, Catherine J
Eisenberg, Burton L
Coleman, William B
Kinlaw, William B #
Issue Date: Mar-2011
Publisher: American Association for Cancer Research, Inc.
Series Title: Molecular Cancer Therapeutics vol:10 issue:3 pages:427-36
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.
ISSN: 1535-7163
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Laboratory of Lipid Metabolism and Cancer (+)
× corresponding author
# (joint) last author

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