Gazi M H, Ito M
Department of Pathology, Yamagata University School of Medicine, Japan.
Cancer Res. 1999 Mar 1;59(5):1115-9.
The mechanism whereby some lymphomas invade liver extensively has not been fully investigated. There is no basement membrane under the sinusoidal endothelium of the liver, and hepatocytes produce fibronectin (FN); therefore, adhesion to this FN may be particularly important for liver infiltration by lymphoma cells. A mouse lymphoma cell line, RL-male1, adhered to FN. However, this cell line did not express classical FN receptors such as very late antigen (VLA)-4 and VLA-5, as estimated by immunofluorescent staining. We have generated monoclonal antibodies (mAbs) that inhibit adhesion of RL-male1 cells to FN. Western blot and immunoprecipitation analyses showed that the new mAbs recognize a protein with an approximate molecular weight of 55,000 (p55). This antigenic protein was highly purified by immunoprecipitation and processed for microsequencing. From NH2-terminal sequence results, the p55 antigen was not identical to known FN receptors. Radioisotope-labeled RL-male1 cells, when injected i.v. into mice, rapidly infiltrated the liver (30-35% of injected cells), as measured by a gamma counter. Intravenous injection of the new mAbs partially (20%) blocked the infiltration of i.v.-injected lymphoma cells into the liver, whereas control rat IgG and an anti-CD11a mAb did not. These results demonstrate that the mouse lymphoma cell line RL-male1 nses a novel FN receptor for liver infiltration.
某些淋巴瘤广泛侵袭肝脏的机制尚未得到充分研究。肝脏窦状内皮细胞下方没有基底膜,且肝细胞可产生纤连蛋白(FN);因此,与这种FN的黏附对于淋巴瘤细胞浸润肝脏可能尤为重要。一种小鼠淋巴瘤细胞系RL-male1可黏附于FN。然而,通过免疫荧光染色估计,该细胞系不表达经典的FN受体,如极迟抗原(VLA)-4和VLA-5。我们制备了可抑制RL-male1细胞与FN黏附的单克隆抗体(mAb)。蛋白质印迹和免疫沉淀分析表明,新的mAb识别一种分子量约为55,000的蛋白质(p55)。通过免疫沉淀对这种抗原性蛋白质进行了高度纯化,并进行微量测序处理。根据氨基末端序列结果,p55抗原与已知的FN受体不同。静脉注射放射性同位素标记的RL-male1细胞后,通过γ计数器测量发现,这些细胞迅速浸润肝脏(占注射细胞的30 - 35%)。静脉注射新的mAb可部分(20%)阻断静脉注射的淋巴瘤细胞浸润肝脏,而对照大鼠IgG和抗CD11a mAb则无此作用。这些结果表明,小鼠淋巴瘤细胞系RL-male1利用一种新的FN受体浸润肝脏。