Molecular Pathology of Glycosyltransferases Involved in the Progression of Colorectal Cancer

上皮细胞的肿瘤性转化伴随着细胞表面碳水化合物的改变，其中许多糖类可以被特异性抗体检测到，从而提供与肿瘤相关的抗原。近年来，研究表明唾液酸化Lewis X的表达与结直肠癌患者的不良预后呈正相关，本课题研究了两种特殊的糖基转移酶：核心2β1，6-乙酰氨基葡萄糖转移酶(C2GnT)和β1，4-半乳糖基转移酶-L(β4GalT-L)在结直肠癌中的临床病理意义。C2GnT是O-葡聚糖生物合成的关键酶，β4GalT-L是N-葡聚糖连接的N-乙酰乳糖胺生物合成的关键酶。结果表明，β4Gall-L在结直肠腺瘤向癌变过程中的表达水平显著增强。此外，还发现C2GnT在结直肠癌中的表达与癌细胞的血管侵袭和侵袭深度呈正相关。这些结果有力地表明这些糖基转移酶在结直肠癌的发生和发展中起着重要的作用。

Neoplastic transformation of epithelial cells is accompanied by alterations of the cell-surface carbohydrates, and many of them can be detected by specific antibodies, thus providing tumor-associated antigens. Recently, it was shown that sialyl Lewis X expressed on the colorectal cancer cells is positively correlated with the poor prognosis of the patients.In this project, we have investigated the clinicopathological significance of two particular glycosyltransreareases, core 2 β1,6-N-acetylglucosaminyltransfearase (C2GnT) and β1,4-galactosyltransferase-l (β4GalT-l) in the colorectal tumors. C2GnT is a key enzyme of the O-glycan biosynthesis, and β4GalT-l is a key enzyme for the biosynthesis of N-acetyllactosamine attached to N-glycans. As results, we have shown that the expression level of β4Gall-l was significantly enhanced during the progression of colorectal adenoma to cancer. In addition, it was also demonstrated that the expression of C2GnT in colorectal cancers was positively correlated with the vessel invasion and depth of invasion of the cancer cells. These results altogether strongly suggest that these glycosyltransferases play important roles for the pathogenesis and progression of colorectal cancer.