School of Biology and the Petit Institute for Bioscience and Bioengineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332-0363, USA.
Mol Cancer. 2010 Jul 12;9:186. doi: 10.1186/1476-4598-9-186.
Sulfatides (ST) are a category of sulfated galactosylceramides (GalCer) that are elevated in many types of cancer including, possibly, ovarian cancer. Previous evidence for elevation of ST in ovarian cancer was based on a colorimetric reagent that does not provide structural details and can also react with other lipids. Therefore, this study utilized mass spectrometry for a structure-specific and quantitative analysis of the types, amounts, and tissue localization of ST in ovarian cancer, and combined these findings with analysis of mRNAs for the relevant enzymes of ST metabolism to explore possible mechanisms.
Analysis of 12 ovarian tissues graded as histologically normal or having epithelial ovarian tumors by liquid chromatography electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS) established that most tumor-bearing tissues have higher amounts of ST. Because ovarian cancer tissues are comprised of many different cell types, histological tissue slices were analyzed by matrix-assisted laser desorption ionization-tissue-imaging MS (MALDI-TIMS). The regions where ST were detected by MALDI-TIMS overlapped with the ovarian epithelial carcinoma as identified by H & E staining and histological scoring. Furthermore, the structures for the most prevalent species observed via MALDI-TIMS (d18:1/C16:0-, d18:1/C24:1- and d18:1/C24:0-ST) were confirmed by MALDI-TIMS/MS, whereas, a neighboring ion(m/z 885.6) that was not tumor specific was identified as a phosphatidylinositol. Microarray analysis of mRNAs collected using laser capture microdissection revealed that expression of GalCer synthase and Gal3ST1 (3'-phosphoadenosine-5'-phosphosulfate:GalCer sulfotransferase) were approximately 11- and 3.5-fold higher, respectively, in the ovarian epithelial carcinoma cells versus normal ovarian stromal tissue, and they were 5- and 2.3-fold higher in comparison with normal surface ovarian epithelial cells, which is a likely explanation for the higher ST.
This study combined transcriptomic and lipidomic approaches to establish that sulfatides are elevated in ovarian cancer and should be evaluated further as factors that might be important in ovarian cancer biology and, possibly, as biomarkers.
硫酸酯（ST）是一类硫酸化半乳糖神经酰胺（GalCer），在包括卵巢癌在内的许多类型的癌症中升高。以前关于卵巢癌中 ST 升高的证据是基于一种不能提供结构细节的比色试剂，并且也可以与其他脂质反应。因此，本研究利用质谱法对卵巢癌中 ST 的类型、数量和组织定位进行了结构特异性和定量分析，并将这些发现与 ST 代谢相关酶的 mRNA 分析相结合，以探讨可能的机制。
通过液相色谱电喷雾电离串联质谱（LC ESI-MS/MS）对 12 个组织进行分析，这些组织被分级为组织学正常或上皮性卵巢肿瘤，结果表明大多数肿瘤组织中 ST 的含量更高。由于卵巢癌组织由许多不同的细胞类型组成，因此通过基质辅助激光解吸电离-组织成像质谱（MALDI-TIMS）对组织切片进行了分析。MALDI-TIMS 检测到的 ST 区域与 H&E 染色和组织学评分确定的卵巢上皮性癌相重叠。此外，通过 MALDI-TIMS/MS 证实了 MALDI-TIMS 观察到的最常见物种（d18:1/C16:0-、d18:1/C24:1-和 d18:1/C24:0-ST）的结构，而不是肿瘤特异性的相邻离子（m/z 885.6）被鉴定为磷脂酰肌醇。使用激光捕获显微切割收集的 mRNA 的微阵列分析显示，GalCer 合酶和 Gal3ST1（3'-磷酸腺苷-5'-磷酸硫酸：GalCer 硫酸转移酶）的表达在卵巢上皮性癌细胞中分别约为正常卵巢基质组织的 11 倍和 3.5 倍，与正常表面卵巢上皮细胞相比分别高 5 倍和 2.3 倍，这可能是 ST 升高的原因。
本研究结合了转录组学和脂质组学方法，证实硫酸酯在卵巢癌中升高，应该进一步评估其作为卵巢癌生物学中可能重要的因素，并且可能作为生物标志物。
