Lipoprotein lipase links dietary fat to solid tumor cell proliferation.
Lipoprotein lipase links dietary fat to solid tumor cell proliferation.
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DOI：
10.1158/1535-7163.mct-10-0802
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发表时间：
2011-03
影响因子：
5.7
通讯作者：
Kinlaw WB
中科院分区：
文献类型：
--
作者：
Kuemmerle NB;Rysman E;Lombardo PS;Flanagan AJ;Lipe BC;Wells WA;Pettus JR;Froehlich HM;Memoli VA;Morganelli PM;Swinnen JV;Timmerman LA;Chaychi L;Fricano CJ;Eisenberg BL;Coleman WB;Kinlaw WB
许多类型的癌细胞需要脂肪酸（FA）的供应来生长和存活，并且在模型系统中中断从头合成FA会产生有效的抗癌作用。我们假设，除了合成外，癌细胞可能通过从血液中摄取预先形成的饮食来源的脂肪酸。这将需要通过分泌酶脂蛋白脂肪酶（LPL）水解循环脂蛋白颗粒中的甘油三酯释放FA，并表达CD36（细胞摄取FA的通道）。我们发现选定的乳腺癌和肉瘤细胞表达和分泌活性LPL，并且都表达CD36。我们进一步证明，在富含甘油三酯的脂蛋白存在下，LPL加速了这些细胞的生长。向表达低水平酶的前列腺癌细胞提供LPL并没有促进生长，但确实阻止了FA合成抑制的细胞毒性作用。此外，LPL敲低抑制HeLa细胞生长。与细胞系相比，免疫组化分析证实LPL和CD36存在于大多数乳腺、脂肪肉瘤和前列腺肿瘤组织中（n = 181）。这些发现表明，除了重新生成脂肪外，癌细胞还可以利用LPL和CD36通过脂肪分解从循环中获取FA，这可以促进它们的生长。干扰饮食中的脂肪摄入、脂肪分解和/或脂肪酸摄取将是必要的，以满足癌细胞对FA的需求。
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 pre-formed, diet-derived fatty acids 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 demonstrate 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 fatty acid uptake will be necessary to target the requirement of cancer cells for FA.