Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener¹. It has been proposed that fructose promotes the growth of some tumours directly by serving as a fuel^2,3. Here we show that fructose supplementation enhances tumour growth in animal models of melanoma, breast cancer and cervical cancer without causing weight gain or insulin resistance. The cancer cells themselves were unable to use fructose readily as a nutrient because they did not express ketohexokinase-C (KHK-C). Primary hepatocytes did express KHK-C, resulting in fructolysis and the excretion of a variety of lipid species, including lysophosphatidylcholines (LPCs). In co-culture experiments, hepatocyte-derived LPCs were consumed by cancer cells and used to generate phosphatidylcholines, the major phospholipid of cell membranes. In vivo, supplementation with high-fructose corn syrup increased several LPC species by more than sevenfold in the serum. Administration of LPCs to mice was sufficient to increase tumour growth. Pharmacological inhibition of ketohexokinase had no direct effect on cancer cells, but it decreased circulating LPC levels and prevented fructose-mediated tumour growth in vivo. These findings reveal that fructose supplementation increases circulating nutrients such as LPCs, which can enhance tumour growth through a cell non-autonomous mechanism.

在过去的五十年里，果糖的消费量大幅增加，这主要是由于高果糖玉米糖浆作为甜味剂的广泛使用¹。有人提出，果糖通过作为燃料直接促进一些肿瘤的生长^2,3。在这里，我们表明，在黑色素瘤、乳腺癌和宫颈癌的动物模型中，果糖补充剂可以增强肿瘤生长，而不会导致体重增加或胰岛素抵抗。癌细胞本身无法轻易使用果糖作为营养物质，因为它们不表达酮糖激酶-C （KHK-C）。原代肝细胞确实表达 KHK-C，导致果溶和多种脂质种类的排泄，包括溶血磷脂酰胆碱 （LPC）。在共培养实验中，肝细胞来源的 LPC 被癌细胞消耗并用于生成磷脂酰胆碱，磷脂酰胆碱是细胞膜的主要磷脂。在体内，补充高果糖玉米糖浆使血清中的几种 LPC 物种增加了 7 倍以上。对小鼠施用 LPC 足以增加肿瘤生长。酮糖激酶的药理学抑制对癌细胞没有直接影响，但它降低了循环 LPC 水平并阻止了果糖介导的体内肿瘤生长。这些发现表明，果糖补充剂会增加 LPC 等循环营养物质，这可以通过细胞非自主机制促进肿瘤生长。