Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.
Glycoconj J. 2013 Aug;30(6):585-97. doi: 10.1007/s10719-012-9458-2. Epub 2012 Dec 15.
Expression and implication of carbohydrate antigens in squamous cell carcinomas (SCCs) in oral cavity was examined. In the cell lines, type 2H and Lewis y antigens were markedly expressed. In the tissues from SCC patients and benign disorders, type 2H was highly expressed in hyperplasia (96.4 %), displasia (92.9 %) and SCC (100 %). Lewis y was, in turn, expressed mainly in cancer tissues (91.3 %), suggesting that Lewis y is a cancer-associated antigen. Normal oral mucosa showed no expression of these blood group antigens. Surprisingly, Lewis y antigen disappeared in the invasion sites where Ki-67 was definitely stained. Over-expression of Lewis y with manipulation of a fucosyltransferase cDNA resulted in suppression of cell growth and invasion, and knockdown of Lewis y also brought about increased cell growth and invasion. In either situations, no changes in the expression of sialyl-Lewis x could be found. Lowered tumor growth and invasion into surrounding tissues were also shown in Lewis y-positive SCC grafts in nu/nu mice. All these results together with alternative staining between Lewis y and Ki-67 in cancer tissues and FUT1 transfectants suggested that loss of Lewis y is a crucial event for the late stage of SCCs.
研究了口腔鳞状细胞癌(SCC)中碳水化合物抗原的表达及其意义。在细胞系中,2H 型和 Lewis y 抗原明显表达。在 SCC 患者和良性病变组织中,2H 型在增生(96.4%)、发育不良(92.9%)和 SCC(100%)中高度表达。相反,Lewis y 主要在癌组织中表达(91.3%),提示 Lewis y 是一种癌相关抗原。正常口腔黏膜不表达这些血型抗原。令人惊讶的是,Lewis y 抗原在 Ki-67 明显染色的侵袭部位消失。用岩藻糖基转移酶 cDNA 操纵 Lewis y 的过表达导致细胞生长和侵袭的抑制,而敲低 Lewis y 也导致细胞生长和侵袭的增加。在这两种情况下,都未发现唾液酸化-Lewis x 的表达发生变化。Lewis y 阳性 SCC 移植物在 nu/nu 小鼠中也显示出肿瘤生长和侵袭周围组织的减少。所有这些结果以及癌症组织和 FUT1 转染子中 Lewis y 和 Ki-67 之间的替代染色表明,Lewis y 的丢失是 SCC 晚期的一个关键事件。