Fatty Foods Grow Your Breast Cancer Cells – The link between high-fat diets, obesity, and cancer has grown stronger over the past several years. Yet, the underlying molecular mechanisms have been slow to surface. Now, investigators from Dartmouth College and the Dartmouth-Hitchcock Norris Cotton Cancer Center set out to understand how fat from the diet might influence breast cancer (BC) cells.
Interestingly, the researchers found that in addition to making new fat to fuel proliferation, breast cancer cells can take up large quantities of fat derived from the lipid-rich particles that circulate in the bloodstream.
Findings from the new study—published recently in the Journal of Lipid Research through an article titled “Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells”—showed that particles bind to the breast cancer cell surface and are then taken into the cell by a novel mechanism not previously described in cancer cells.
This uptake provides a large supply of the fat that drives the proliferation of the cancer cells.
“We previously showed that fatty particles in the bloodstream may augment the growth of breast cancer cells,” explained senior study investigator William Kinlaw, MD, emeritus professor of medicine at Dartmouth’s Geisel School of Medicine, and member of the cancer biology and therapeutics research program at Dartmouth’s Norris Cotton Cancer Center.
“Our new work demonstrates that breast cancer cells can engulf large amounts of preformed fat from the blood using an unexpected mechanism of fat particle uptake called ‘endocytosis of lipoproteins’.” The uptake results in metabolic reprogramming of the cells to take advantage of this “free lunch” and reveals a direct connection between dietary fat and cancer cell biology.
The authors go on to explain that “a model in which lipoprotein lipase (LPL) is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the very low-density lipoprotein (VLDL) receptor to internalize VLDLs via receptor-mediated endocytosis.
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We also demonstrated that gene expression programs for lipid synthesis vs uptake respond robustly to TG-rich lipoprotein availability.”
The literature has also largely focused on the manufacture of new fat by cancer cells as a therapeutic target. Many academic- and pharma-based efforts are underway to target the synthesis of new fat by cancer cells.
“The literature emphasizes de novo fatty acid synthesis and exogenous free fatty acid uptake using CD36 as paramount mechanisms for lipid acquisition by cancer cells,” the authors noted.
“We find that the uptake of intact lipoproteins is also an important mechanism for lipid acquisition, and that the relative reliance on lipid synthesis vs uptake varies among BC cell lines and in response to VLDL availability.”
The research team concluded that “this metabolic plasticity has important implications for the development of therapies aimed at the lipid dependence of many types of cancer, in that inhibition of fatty acid synthesis, may elicit compensatory upregulation of lipid uptake.
Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.”