脂滴储存促进小鼠胰腺肿瘤生长。
Lipid droplet storage promotes murine pancreatic tumor growth.
机构信息
Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
出版信息
Oncol Rep. 2021 Apr;45(4). doi: 10.3892/or.2021.7972. Epub 2021 Mar 2.
Hypoxia Inducible Lipid Droplet Associated (HILPDA) is frequently overexpressed in tumors and promotes neutral lipid storage. The impact of Hilpda on pancreatic ductal adenocarcinoma (PDAC) tumor growth is not known. In order to evaluate Hilpda‑dependent lipid storage mechanisms, expression of Hilpda in murine pancreatic cells (KPC) was genetically manipulated. Lipid droplet (LD) abundance and triglyceride content were measured, and model tumor growth in nu/nu mice was determined. The results showed that excess lipid supply increased triglyceride storage and LD formation in KPC cells in a HILPDA‑dependent manner. Contrary to published results, inhibition of Adipose Triglyceride Lipase (ATGL) did not ameliorate the triglyceride abundance differences between Hilpda WT and KO cells. Hilpda ablation significantly decreased the growth rate of model tumors in immunocompromised mice. In conclusion, Hilpda is a positive regulator of triglyceride storage and lipid droplet formation in murine pancreatic cancer cells and lipid accumulation and tumor growth . Our data suggest that deregulated ATGL is not responsible for the absence of LDs in KO cells in this context.
缺氧诱导的脂滴相关蛋白（HILPDA）在肿瘤中常过度表达，并促进中性脂质的储存。然而，Hilpda 对胰腺导管腺癌（PDAC）肿瘤生长的影响尚不清楚。为了评估 Hilpda 依赖性脂质储存机制，本研究对小鼠胰腺细胞（KPC）中的 Hilpda 进行了基因操作。测量了脂滴（LD）的丰度和甘油三酯含量，并在 nu/nu 小鼠中确定了模型肿瘤的生长情况。结果表明，过量的脂质供应以 HILPDA 依赖的方式增加了 KPC 细胞中的甘油三酯储存和 LD 形成。与已发表的结果相反，抑制脂肪甘油三酯脂肪酶（ATGL）并没有改善 Hilpda WT 和 KO 细胞之间甘油三酯丰度的差异。Hilpda 缺失显著降低了免疫缺陷小鼠模型肿瘤的生长速度。综上所述，Hilpda 是小鼠胰腺癌细胞中甘油三酯储存和脂滴形成的正调节剂，并且与脂滴积累和肿瘤生长有关。我们的数据表明，在这种情况下，失活的 ATGL 并不是 KO 细胞中缺乏 LD 的原因。
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