Knockdown of Mgat5 inhibits breast cancer cell growth with activation of CD4+ T cells and macrophages
Knockdown of Mgat5 inhibits breast cancer cell growth with activation of CD4+ T cells and macrophages
复制标题
敲低 Mgat5 可通过激活 CD4 T 细胞和巨噬细胞抑制乳腺癌细胞生长
DOI：
10.4049/jimmunol.180.5.3158
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发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Zhang, Xiao-Lian
中科院分区：
文献类型：
--
作者：
Li, Dongqing;Li, Yanmei;Zhang, Xiao-Lian
N-乙酰葡糖胺转移酶V（Mgat 5或GnT-V）是一种催化细胞蛋白天冬酰胺（N）连接寡糖\（N-聚糖）上N-乙酰葡糖胺的β 1-6分支的酶。Mgat 5聚糖产物的水平通常在恶性肿瘤中增加。尽管已知Mgat 5在肿瘤转移中很重要，但Mgat 5对宿主免疫反应的影响尚未完全确定。在这项研究中，Mgat 5特异性短发夹RNA（shRNA）载体转染到小鼠乳腺癌MA 782细胞中，以评估Mgat 5对肿瘤细胞生长，T细胞和巨噬细胞接种shRNA转染的癌细胞后的影响。结果表明，阻断MA 782细胞中Mgat 5修饰的聚糖的表达在体内和体外均显著抑制肿瘤进展，强烈刺激Th 1细胞因子产生，并增强体内巨噬细胞的调理吞噬能力。重要的是，通过Mgat 5-shRNA减少MA 782肿瘤细胞上的复合N-聚糖导致CD 4（+）T细胞的增殖和CD 45表面表达显著增加。我们的数据表明Mgat 5-shRNA可以作为一个有用的工具来治疗乳腺癌，以及一个强大的工具，N-聚糖和糖蛋白合成的功能研究。我们的数据表明，敲低Mgat 5抑制乳腺癌细胞的生长，激活CD 4（+）T细胞和巨噬细胞。
N-acetylglucosaminyltransferase V (Mgat5 or GnT-V) is an enzyme that catalyzes beta 1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides\(N-glycan) of cell proteins. The levels of Mgat5 glycan products commonly are increased in malignancies. Although Mgat5 is known to be important in tumor metastases, the effects of Mgat5 on host immune responses are not fully defined. In this study, a Mgat5 specific-short hairpin RNA (shRNA) vector was transfected into murine mammary adenocarcinoma MA782 cells to assess the effects of Mgat5 on tumor cell growth, T cells, and macrophages following inoculation of mice with shRNA-transfected cancer cells. The results showed that blocking expression of Mgat5-modified glycans in MA782 cells significantly suppressed tumor progression both in vivo and in vitro, strongly stimulated Th1 cytokine production, and enhanced opsonophagocytic capability of macrophages in vivo. Importantly, reduction of complex N-glycans on MA782 tumor cells by Mgat5-shRNA resulted in significantly increased proliferation and CD45 surface expression of CD4(+) T cells. Our data suggest Mgat5-shRNA could serve as a useful tool to treat breast cancer as well as a powerful tool for the functional investigation of N-glycans and glycoprotein synthesis. Our data suggest that knockdown of Mgat5 inhibits breast cancer cells' growth with activation of CD4(+) T cells and macrophages.