PDF(Pubmed)
Abstract：
The immunoglobulin superfamily (IgSF) is one of the largest families of cell-surface molecules involved in various cell-cell interactions, including cancer-stromal interactions. In this study, we undertook a comprehensive RT-PCR-based screening for IgSF molecules that promote experimental lung metastasis in mice. By comparing the expression of 325 genes encoding cell-surface IgSF molecules between mouse melanoma B16 cells and its highly metastatic subline, B16F10 cells, we found that expression of the immunoglobulin superfamily member 3 gene (Igsf3) was significantly enhanced in B16F10 cells than in B16 cells. Knockdown of Igsf3 in B16F10 cells significantly reduced lung metastasis following intravenous injection into C57BL/6 mice. IGSF3 promoted adhesion of B16F10 cells to vascular endothelial cells and functioned as a homophilic cell adhesion molecule between B16F10 cells and vascular endothelial cells. Notably, the knockdown of IGSF3 in either B16F10 cells or vascular endothelial cells suppressed the transendothelial migration of B16F10 cells. Moreover, IGSF3 knockdown suppressed the extravasation of B16F10 cells into the lungs after intravenous injection. These results suggest that IGSF3 promotes the metastatic potential of B16F10 cells in the lungs by facilitating their adhesion to vascular endothelial cells.
摘要：
免疫球蛋白超家族（IgSF）是参与各种细胞-细胞相互作用的最大的细胞表面分子家族之一，包括癌症-基质相互作用。在这项研究中,我们对促进小鼠实验性肺转移的IgSF分子进行了全面的基于RT-PCR的筛选。通过比较小鼠黑色素瘤B16细胞及其高转移亚系中编码细胞表面IgSF分子的325个基因的表达，B16F10细胞，我们发现免疫球蛋白超家族成员3基因(Igsf3)在B16F10细胞中的表达比在B16细胞中显著增强。B16F10细胞中Igsf3的敲低可显著减少C57BL/6小鼠静脉注射后的肺转移。IGSF3促进B16F10细胞与血管内皮细胞的粘附，并在B16F10细胞与血管内皮细胞之间起同源细胞粘附分子的作用。值得注意的是,B16F10细胞或血管内皮细胞中IGSF3的敲减抑制了B16F10细胞的跨内皮迁移。此外，IGSF3敲低抑制静脉注射后B16F10细胞向肺的外渗。这些结果表明，IGSF3通过促进B16F10细胞与血管内皮细胞的粘附来促进其在肺中的转移潜力。
