SUPPRESSION OF LUNG METASTASIS OF B16 MOUSE MELANOMA BY N-ACETYLGLUCOSAMINYLTRANSFERASE-III GENE TRANSFECTION
SUPPRESSION OF LUNG METASTASIS OF B16 MOUSE MELANOMA BY N-ACETYLGLUCOSAMINYLTRANSFERASE-III GENE TRANSFECTION
复制标题
DOI：
10.1073/pnas.92.19.8754
复制
发表时间：
1995-09-12
影响因子：
11.1
通讯作者：
TANIGUCHI, N
中科院分区：
文献类型：
--
作者：
YOSHIMURA, M;NISHIKAWA, A;TANIGUCHI, N
由β-1，6-N-乙酰葡糖胺转移酶（GnT-V）形成的N-连接寡糖的β 1-6结构与转移潜能相关。我们建立了一个高转移性的亚克隆，B16-hm，从低转移性B16-F1小鼠黑色素瘤细胞。将编码β-1，4-N-乙酰氨基葡萄糖转移酶（GnT-III）的基因导入B16-hm细胞中，获得了3个稳定表达高活性GnT-III的克隆。在这些转染子中，对白细胞凝集性植物血凝素的亲和力降低，而对白细胞凝集性光血凝素的结合增加，表明β 1-6结构由于内在GnT-V和异位表达的GnT-III之间对底物的竞争而降低。在静脉注射转染子到同基因小鼠和裸鼠中后，肺转移被显著抑制，这表明β 1-6结构的减少通过独立于鼠系统的机制抑制转移。这些转染子还显示对基质胶的侵袭力降低，并抑制细胞对胶原和层粘连蛋白的附着，细胞生长不受影响。我们的研究结果表明，β 1-6分支在转移的外渗阶段的侵袭和细胞附着中起着致病作用。
The beta 1-6 structure of N-linked oligosaccharides, formed by beta-1,6-N-acetylglucosaminyltransferase (GnT-V), is associated with metastatic potential. We established a highly metastatic subclone, B16-hm, from low metastatic B16-F1 murine melanoma cells. The gene encoding beta-1,4-N-acetylglucosaminyltransferase (GnT-III) was introduced into the B16-hm cells, and three clones that stably expressed high GnT-III activity were obtained. In these transfectants, the affinity to leukoagglutinating phytohemagglutinin was reduced, whereas the binding to erythro agglutinating photohemagglutinin was increased,indicating beta 1-6 structure was decreased due to competition for substrate between intrinsic GnT-V and ectopically expressed GnT-III. Lung metastasis after intravenous injection of the transfectants into syngeneic and nude mice was significantly suppressed, suggesting that the decrease in beta 1-6 structure suppressed metastasis via a mechanism independent of the murine system. These transfectants also displayed decreased invasiveness into Matrigel and inhibited cell attachment to collagen and laminin, Cell growth was not affected. Our results demonstrate a causative role for beta 1-6 branches in invasion and cell attachment in the extravasation stage of metastasis.