Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA.
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
J Mass Spectrom. 2022 Aug;57(8):e4880. doi: 10.1002/jms.4880.
Altered lipid metabolism is one of the hallmarks of cancer. Cellular proliferation and de novo synthesis of lipids are related to cancer progression. In this study, we evaluated the lipidomic profile of two-dimensional (2D) monolayer and multicellular tumor spheroids from the HCT 116 colon carcinoma cell line. We utilized serial trypsinization on the spheroid samples to generate three cellular populations representing the proliferative, quiescent, and necrotic regions of the spheroid. This analysis enabled a comprehensive identification and quantification of lipids produced in each of the spheroid layer and 2D cultures. We show that lipid subclasses associated with lipid droplets form in oxygen-restricted and acidic regions of spheroids and are produced at higher levels than in 2D cultures. Additionally, sphingolipid production, which is implicated in cell death and survival pathways, is higher in spheroids relative to 2D cells. Finally, we show that increased numbers of lipids composed of polyunsaturated fatty acids (PUFAs) are produced in the quiescent and necrotic regions of the spheroid. The lipidomic signature for each region and cell culture type highlights the importance of understanding the spatial aspects of cancer biology. These results provide additional lipid biomarkers in colon cancer cells that can be further studied to target pivotal lipid production pathways.
脂质代谢改变是癌症的特征之一。细胞增殖和新合成的脂质与癌症的进展有关。在这项研究中，我们评估了 HCT 116 结肠癌细胞系的二维（2D）单层和多细胞肿瘤球体的脂质组学特征。我们利用球体样本的连续胰蛋白酶消化来产生代表球体增殖、静止和坏死区域的三种细胞群体。这种分析能够全面识别和定量每个球体层和 2D 培养物中产生的脂质。我们表明，与脂滴相关的脂质亚类在球体的缺氧和酸性区域形成，并以高于 2D 培养物的水平产生。此外，与细胞死亡和存活途径有关的鞘脂的产生在球体中相对 2D 细胞更高。最后，我们表明，在球体的静止和坏死区域中，由多不饱和脂肪酸（PUFA）组成的脂质数量增加。每个区域和细胞培养类型的脂质组学特征突出了理解癌症生物学空间方面的重要性。这些结果为结肠癌细胞提供了额外的脂质生物标志物，可以进一步研究以靶向关键的脂质产生途径。
