Departments of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Int J Gynecol Cancer. 2012 Sep;22(7):1192-7. doi: 10.1097/IGC.0b013e31825f639f.
It is well known that a poorly differentiated endometrial adenocarcinoma shows more rapid progression and a worse response to therapy than a well-differentiated endometrial adenocarcinoma. Qualitative and quantitative changes of cell surface glycolipids occur during neoplastic transformation. Sulfatide is one of the sulfated glycolipids in the cell membrane that may have an important role in various functions such as cell adhesion. To examine the molecular background of the morphological and biological features of well-differentiated and poorly differentiated cancer, we measured the levels of lipids, especially glycolipids, in tumor tissues from patients with endometrial carcinoma.
We determined the composition of lipids and glycolipids in tumor tissues, investigated glycosyltransferase messenger RNA expression by the reverse transcription-polymerase chain reaction, and assessed the localization of galactosylceramide sulfotransferase (an enzyme involved in sulfatide biosynthesis) by immunohistochemical staining.
No significant differences were observed between well-differentiated and poorly differentiated cancer with respect to the levels of cholesterol ester, cholesterol, phospholipids, cholesterol sulfate, ceramides, neutral glycolipids of the globo series, and GM3 ganglioside. However, the amount of sulfatides in well-differentiated tumors was significantly greater than that in poorly differentiated tumors, which was confirmed by thin-layer chromatography and immunostaining with a monoclonal antisulfatide antibody. Altered expression of sulfatide was found to be secondary to a change of galactosylceramide sulfotransferase messenger RNA expression. Immunohistochemical staining revealed that galactosylceramide sulfotransferase expression was characteristically observed in glandular areas but not in solid areas.
These findings suggest that sulfatide contributes to the well-differentiated phenotype of endometrial adenocarcinoma and that it is being expressed in normal uterine endometrium at sites of gland formation during the luteal phase, as we have previously reported.
众所周知，低分化子宫内膜腺癌比高分化子宫内膜腺癌具有更快的进展速度和更差的治疗反应。细胞表面糖脂的定性和定量变化发生在肿瘤转化过程中。硫酸脑苷脂是细胞膜中一种硫酸化糖脂，可能在细胞黏附等多种功能中发挥重要作用。为了研究高分化和低分化癌的形态和生物学特征的分子背景，我们测量了子宫内膜癌患者肿瘤组织中的脂质，特别是糖脂的水平。
我们测定了肿瘤组织中脂质和糖脂的组成，通过反转录-聚合酶链反应（RT-PCR）检测糖苷转移酶信使 RNA 的表达，并通过免疫组织化学染色评估半乳糖基神经酰胺硫酸转移酶（一种参与硫酸脑苷脂生物合成的酶）的定位。
高分化和低分化癌之间，胆固醇酯、胆固醇、磷脂、胆固醇硫酸盐、神经酰胺、globoside 系列的中性糖脂和 GM3 神经节苷脂的水平没有显著差异。然而，高分化肿瘤中的硫酸脑苷脂含量明显高于低分化肿瘤，这通过薄层层析和用单克隆抗硫酸脑苷脂抗体进行免疫染色得到证实。硫酸脑苷脂表达的改变是由于半乳糖基神经酰胺硫酸转移酶信使 RNA 表达的改变所致。免疫组织化学染色显示，半乳糖基神经酰胺硫酸转移酶表达的特征是在腺区而不是在实性区观察到。
这些发现表明，硫酸脑苷脂有助于子宫内膜腺癌的高分化表型，并且如我们之前报道的那样，在黄体期子宫子宫内膜的腺体形成部位表达。
