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层粘连蛋白α3B链在正常人体组织血管和上皮基底膜中的定位及其在皮肤癌中的下调。

Localization of laminin alpha3B chain in vascular and epithelial basement membranes of normal human tissues and its down-regulation in skin cancers.

作者信息

Kariya Yoshinobu, Mori Taizo, Yasuda Chie, Watanabe Naoko, Kaneko Yoshie, Nakashima Yukiko, Ogawa Takashi, Miyazaki Kaoru

机构信息

Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama, 244-0813, Japan.

出版信息

J Mol Histol. 2008 Aug;39(4):435-46. doi: 10.1007/s10735-008-9183-0. Epub 2008 Aug 1.

Abstract

The basement membrane (BM) proteins laminins, which consist of alpha, beta and gamma chains, play critical roles in the maintenance of tissue structures. One of laminin alpha chains, alpha3 has two isoforms, the truncated form alpha3A and the full-sized form alpha3B. In contrast to alpha3A laminins, little is known about alpha3B laminins. To show the histological distribution of the laminin alpha3B chain, we prepared alpha3B-specific monoclonal antibodies. Immunohistochemical analysis showed that the alpha3B chain was colocalized with the alpha3A, beta3 and gamma2 chains in the epithelial BMs of the skin, esophagus, breast and lung, suggesting the presence of laminin-3B32 (laminin-5B) and laminin-3A32 (laminin-5A). In the lung alveoli, laminin-3B32 was dominant over laminin-3A32, but vice versa in other epithelial BMs. In contrast, the BMs of blood vessels including capillaries were strongly positive for alpha3B, but almost or completely negative for alpha3A, beta3 and gamma2. alpha3B was colocalized with beta1 and gamma1 in these BMs. The alpha3B chain was scarcely detected in the vessels of malignant skin cancers, though the gamma2 and beta3 chains were highly expressed in the cancer cells. These results strongly suggest that the laminin alpha3B chain is widely expressed in vascular BMs of normal tissues, probably as laminin-3B11/3B21 (laminin-6B/7B).

摘要

由α、β和γ链组成的基底膜(BM)蛋白层粘连蛋白在组织结构维持中发挥关键作用。层粘连蛋白α链之一的α3有两种异构体,截短形式的α3A和全长形式的α3B。与α3A层粘连蛋白相比,关于α3B层粘连蛋白的了解甚少。为了显示层粘连蛋白α3B链的组织学分布,我们制备了α3B特异性单克隆抗体。免疫组织化学分析表明,α3B链与α3A、β3和γ2链在皮肤、食管、乳腺和肺的上皮基底膜中共定位,提示存在层粘连蛋白-3B32(层粘连蛋白-5B)和层粘连蛋白-3A32(层粘连蛋白-5A)。在肺泡中,层粘连蛋白-3B32比层粘连蛋白-3A32占优势,但在其他上皮基底膜中则相反。相比之下,包括毛细血管在内的血管基底膜对α3B呈强阳性,但对α3A、β3和γ2几乎或完全呈阴性。α3B在这些基底膜中与β1和γ1共定位。在恶性皮肤癌的血管中几乎检测不到α3B链,尽管γ2和β3链在癌细胞中高表达。这些结果强烈表明,层粘连蛋白α3B链在正常组织的血管基底膜中广泛表达,可能以层粘连蛋白-3B11/3B21(层粘连蛋白-6B/7B)的形式存在。

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