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人类细胞与肿瘤中的整合素

Integrins in human cells and tumors.

作者信息

Virtanen I, Korhonen M, Kariniemi A L, Gould V E, Laitinen L, Ylänne J

机构信息

Department of Anatomy, University of Helsinki, Finland.

出版信息

Cell Differ Dev. 1990 Dec 2;32(3):215-27. doi: 10.1016/0922-3371(90)90034-t.

DOI:10.1016/0922-3371(90)90034-t
PMID:2099238
Abstract

We have studied the distribution of the alpha- and beta-subunits of integrins in developing and adult human kidney as well as in selected other tissues and cultured cells. In cultured cells some of the integrin subunits (beta 1, alpha 1, alpha 2 and alpha 5) colocalize with talin at focal adhesions when plated on an appropriate ligand. Similarly, in tissues the polarization of beta 1-integrins in colocalization with talin appears to indicate adhesive complexes, as demonstrated in adult glomeruli. In human kidney, the alpha subunits of integrins were seen to be segment-specifically expressed already in fetal tissues. In glomeruli the integrin alpha 1 subunit characterized mesangial cells while the alpha 2 and alpha 3 subunits showed immunoreactivity in endothelial cells and podocytes, respectively. In renal tubuli, the alpha 6 subunit, complexed with the beta 1 subunit, showed a typical polarized distribution coaligning with the tubular basement membrane while the alpha 3 and alpha 2 subunits were expressed in distal tubular cells. These results suggested that in kidney the alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 integrins can function as basement membrane receptors. The alpha 5 subunit was nearly lacking in the kidney and it appears to be mainly expressed in some smooth muscle cells. In other tissues distinct patterns in the expression of integrins were found. Thus, in many glandular epithelial cells the alpha 3 beta 1 integrin appeared to function as a basement membrane receptor while in various stratified epithelia and in the breast such a polarized localization could be found for the alpha 6 beta 4 integrin. Finally, although presenting a clearly polarized distribution for beta 1 integrins, none of the alpha subunits could be found in cardiac or skeletal muscle cells and none of the integrins could be revealed in neuronal cells of human developing and adult cerebrum or cerebellum, although neurons in peripheral tissues contained abundantly the alpha 6 beta 1 integrin complex. In human tumors, the tumor cells, including also metastastatic tumors, generally presented the same integrins as their tissues of origin. In some poorly differentiated tumors both a population heterogeneity and even a lack of expression or a disorganization of basement membrane receptor integrins was obvious.

摘要

我们研究了整合素α和β亚基在发育中和成年期的人类肾脏以及其他选定组织和培养细胞中的分布情况。在培养细胞中,当接种在合适的配体上时,一些整合素亚基(β1、α1、α2和α5)在粘着斑处与踝蛋白共定位。同样,在组织中,β1整合素与踝蛋白共定位的极化现象似乎表明存在粘着复合物,如在成年肾小球中所示。在人类肾脏中,整合素的α亚基在胎儿组织中就已呈现出节段特异性表达。在肾小球中,整合素α1亚基可鉴定系膜细胞,而α2和α3亚基分别在内皮细胞和足细胞中显示免疫反应性。在肾小管中,与β1亚基复合的α6亚基呈现出与肾小管基底膜对齐的典型极化分布,而α3和α2亚基在远端肾小管细胞中表达。这些结果表明,在肾脏中,α2β1、α3β1和α6β1整合素可作为基底膜受体发挥作用。α5亚基在肾脏中几乎不存在,它似乎主要在一些平滑肌细胞中表达。在其他组织中发现了整合素表达的不同模式。因此,在许多腺上皮细胞中,α3β1整合素似乎作为基底膜受体发挥作用,而在各种复层上皮和乳腺中,α6β4整合素可呈现这种极化定位。最后,尽管β1整合素呈现出明显的极化分布,但在心肌或骨骼肌细胞中未发现任何α亚基,在人类发育中和成年大脑或小脑的神经元细胞中也未检测到任何整合素,尽管外周组织中的神经元大量含有α6β1整合素复合物。在人类肿瘤中,肿瘤细胞,包括转移性肿瘤,通常呈现出与其起源组织相同的整合素。在一些低分化肿瘤中,群体异质性明显,甚至存在基底膜受体整合素表达缺失或紊乱的情况。

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