Selective localization of matrix metalloproteinase 9, beta1 integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells.
Selective localization of matrix metalloproteinase 9, beta1 integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells.
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发表时间：
1998-10
期刊：
影响因子：
11.2
通讯作者：
V. Dolo;A. Ginestra;Donata Cassarà;S. Violini;G. Lucania;M. Torrisi;H. Nagase;S. Canevari;A. Pavan;M. Vittorelli
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文献类型：
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作者：
V. Dolo;A. Ginestra;Donata Cassarà;S. Violini;G. Lucania;M. Torrisi;H. Nagase;S. Canevari;A. Pavan;M. Vittorelli
膜囊泡从细胞表面脱落被认为是参与细胞-细胞和细胞-基质相互作用以及肿瘤进展的重要过程。通过对8701-BC人乳腺癌细胞表面复制品的免疫电镜分析，我们观察到从质膜脱落的膜囊泡含有密集聚集的明胶酶B [基质金属蛋白酶9（MMP-9）]、β 1整合素和人淋巴细胞抗原I类分子。相比之下，α-叶酸受体均匀分布在光滑的细胞膜和脱落区。只有当细胞在血清存在下培养时，所选分子的细胞表面聚集和膜囊泡释放才明显。囊泡脱落优先发生在细胞的边缘或沿着狭窄的突起。明胶酶谱法也证明了MMP-9前体和MMP-9活性形式在脱落囊泡中的特异性积累。此外，Western印迹分析显示存在大量的proMMP-9/金属蛋白酶1组织抑制剂复合物。富含MMP-9和β 1整合素的质膜的选定区域的释放表明，从肿瘤细胞脱落的膜囊泡在细胞迁移期间细胞外基质的定向蛋白水解中起重要作用。人淋巴细胞抗原I类抗原的存在表明肿瘤细胞逃避免疫监视的机制。
The shedding of membrane vesicles from the cell surface is a vital process considered to be involved in cell-cell and cell-matrix interactions and in tumor progression. By immunoelectron microscopic analysis of surface replicas of 8701-BC human breast carcinoma cells, we observed that membrane vesicles shed from plasma membranes contained densely clustered gelatinase B [matrix metalloproteinase 9 (MMP-9)], beta1 integrins, and human lymphocyte antigen class I molecules. By contrast, alpha-folate receptor was uniformly distributed on the smooth cell membrane and shedding areas. Both cell surface clustering of selected molecules and membrane vesicle release were evident only when cells were cultured in the presence of serum. Vesicle shedding occurred preferentially at the edge or along narrow protrusions of the cell. Specific accumulation of proMMP-9 and active forms of MMP-9 in shed vesicles was also demonstrated by gelatin zymography. In addition, Western blotting analysis showed the presence of a large amount of proMMP-9/tissue inhibitor of metalloproteinase 1 complex. The release of selected areas of plasma membranes enriched with MMP-9 and beta1 integrins indicates that membrane vesicle shedding from tumor cells plays an important role in the directional proteolysis of the extracellular matrix during cellular migration. The presence of human lymphocyte antigen class I antigens suggests a mechanism for tumor cells to escape from immune surveillance.