Department of Surgery and Cancer, Imperial College, London, UK.
Breast Cancer Res Treat. 2010 Nov;124(2):543-9. doi: 10.1007/s10549-010-0968-y. Epub 2010 Jun 10.
Weight gain in women receiving chemotherapy for breast cancer is associated with a higher risk of recurrence. Using metabonomic profiling, we recently reported that plasma lactate and alanine were prognostic for weight gain in individuals with breast cancer receiving chemotherapy. The role of lipid second messengers has not been studied. We assessed serum levels of sphingosine-1-phosphate (S1P), a known secreted lipid second messenger with a role in cell growth, in sequential samples from post-menopausal women receiving standard chemotherapy for early breast cancer and correlated these with body mass measurements and metabonomic profiling. While serum S1P levels prior to treatment did not correlate with body weight changes or circulating alanine and lactate, S1P levels measured during therapy were inversely correlated with weight gain (P = 0.04), but not weight loss (P = 0.74) or no change in weight (P = 0.5), suggesting a role of dynamic circulating S1P in adipocyte growth. These data provide evidence for an association between serum S1P and weight gain during chemotherapy cycles in women with breast cancer. Lipid second messengers have a role in chemotherapy-induced weight gain in breast cancer.
接受乳腺癌化疗的女性体重增加与复发风险增加相关。最近，我们使用代谢组学分析报告称，血浆中的乳酸和丙氨酸水平与接受化疗的乳腺癌患者的体重增加具有预后价值。脂质第二信使的作用尚未得到研究。我们评估了绝经后女性在接受标准化疗治疗早期乳腺癌时的血清神经鞘氨醇-1-磷酸（S1P）水平，这是一种已知的具有细胞生长作用的分泌型脂质第二信使，并将其与体重测量和代谢组学分析相关联。虽然治疗前的血清 S1P 水平与体重变化或循环中的丙氨酸和乳酸无相关性，但治疗期间测量的 S1P 水平与体重增加呈负相关（P = 0.04），而与体重减轻（P = 0.74）或体重无变化（P = 0.5）无关，提示循环 S1P 的动态变化与脂肪细胞生长有关。这些数据为乳腺癌女性在化疗周期中血清 S1P 与体重增加之间的关联提供了证据。脂质第二信使在乳腺癌的化疗诱导性体重增加中发挥作用。
