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Lipoprotein Lipase Links Dietary Fat to Solid Tumor Cell Proliferation
Open accessPublished version of a preprint
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.
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“An elevated expression of lipoprotein lipase (LPL) and monoacylglycerol lipase (MAGL) across diverse cancer subtypes and correlates with invasiveness”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Kuemmerle et al., 2011
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Metadata
- Authors
- Kuemmerle, N. B., Rysman, E., Lombardo, P. S., Flanagan, A. J., Lipe, B. C., Wells, W. A., Pettus, J. R., Froehlich, H. M., Memoli, V. A., Morganelli, P. M., Swinnen, J. V., Timmerman, L. A., Chaychi, L., Fricano, C. J., Eisenberg, B. L., Coleman, W. B., & Kinlaw, W. B.
- Affiliations
- Dartmouth–Hitchcock Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Kinlaw, William B.
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2011-03-01
- Volume
- 10
- Issue
- 3
- Pages
- 427-436
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- PMC
- PMC3074101
- OpenAlex
- W2117594441
- Cited by
- 286
- References
- 46
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 22 · 2023: 20 · 2022: 31 · 2021: 35 · 2020: 24 · 2019: 32 · 2018: 19 · 2017: 16 · 2016: 21 · 2015: 11 · 2014: 9 · 2013: 8 · 2012: 11
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Cancer Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Howard Hughes Medical Institute (52005870)
- Dartmouth College
- Fonds Wetenschappelijk Onderzoek
- Universität Ulm
- Vlaamse regering
- Norris Cotton Cancer Center
- National Cancer Institute (R01CA126618, P50CA058207, P30CA023108)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007508, DK 07508)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- lipoprotein lipase, CD36, fatty acid uptake, dietary fat, solid tumor growth, lipolysis, triglyceride-rich lipoproteins, breast cancer, sarcoma, prostate cancer, fatty acid synthesis inhibition, cancer metabolism
- MeSH terms
- Animals, Dietary Fats, Fatty Acids, Female, Humans, Lipolysis, Lipoprotein Lipase, Liposarcoma, Male, Mice, Transgenic, Neoplasms, CD36 Antigens, Oligonucleotide Array Sequence Analysis, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation, Mice, Fatty Acid Synthesis Inhibitors
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