脂质组成对人胶质瘤细胞系恶性程度的影响

Effects of lipid composition on malignancy of human glioma cell lines

目的:探讨与神经胶质瘤恶性分化演变相关的脂质变化和复杂的脂质代谢网络。方法:选取具有不同成瘤能力和转移潜能的人神经胶质瘤细胞系A172、U251和U87MG,进行总脂抽提,通过Shotgun脂质组学方法进行规模性、整体性的脂质组学分析。结果:对3个人神经胶质瘤细胞系进行大规模脂质定性分析,共鉴定到1541个脂质分子,主要包括甘油磷脂、甘油脂和鞘脂三大类。与无成瘤能力的A172细胞系相比,甘油磷脂PC和PA的表达在恶性胶质母细胞瘤细胞U251和U87MG中呈现显著上调的趋势;含d18∶1的鞘脂(d18∶1SP)则随着胶质瘤成瘤能力和转移潜能的增加表达呈显著降低(P<0.05)。通过定量脂质组学研究,筛选得到121个具有统计学差异变化的脂质分子;并通过多元变量统计分析,揭示差异脂质组成能将具有成瘤和转移能力的细胞系U251和U87MG与无成瘤能力的细胞系A172系区分开来。结论:在成瘤能力和转移潜能不同的胶质瘤细胞系之间存在明显的脂质组成差异,差异表达的脂质可能与神经胶质瘤转移复发有关。

Objective: To explore altered lipid composition and complex metabolic networks associated with malignant differentiation of glioma. Methods: Shotgun lipidomics analyses in a series of human glioma cell lines with different tumorigenicity and metastasis potential, containing non-tumorigenic A172, tumorigenic U251, and metastatic U87MG. Results: A total of 1 541 unique lipids were identified originating from 3 major lipid categories-glycerophospholipids, glycerides, and sphingolipids via systematic lipidomics profiling. Both positive and negative ESI tandem mass spectrometry modes were used, and precursor ion (PI) scans and neutral loss (NL) scans were run respectively in each mode. GP species PC and PA had the increased trends in tumorigenic cell lines U251 and U87MG compared with A172, whereas remarkably decreased d18∶1-containing SP were observed with the increase of glioma tumorigenicity and metastatic potential ( P <0.05). Comparative lipidomics screening revealed 121 significantly changed lipids, and multivariate statistical analyses unraveled that altered lipid composition distinguished tumorigenic and metastatic cell lines U251 and U87MG from non-tumorigenic cell lines A172. Conclusions: Our lipidomics data shows obvious differences in lipid composition between non-tumorigenic and tumorigenic glioma cells. Differentially expressed lipids may be related to glioma metastasis and recurrence. These findings can lead to identify critical diagnostic biomarkers as well as developing therapeutic targets for glioma metastasis and recurrence.