Soluble Lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro
Soluble Lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro
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DOI：
10.1016/j.yexcr.2014.07.012
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发表时间：
2014-10-15
影响因子：
3.7
通讯作者：
Mitaka, Toshihiro
中科院分区：
文献类型：
--
作者：
Kikkawa, Yamato;Miwa, Takahiro;Mitaka, Toshihiro
Lutheran（Lu）是一种免疫球蛋白超家族跨膜受体，也被称为基底细胞粘附分子（B-CAM）。Lu/B-CAM是层粘连蛋白α 5的特异性受体，层粘连蛋白α 5是层粘连蛋白-511（LM-511）的亚基，层粘连蛋白-511是各种组织中基底膜的主要组分。我们的前期研究表明Lu/B-CAM被MT 1-MMP切割并从细胞表面释放。在这项研究中，我们研究了可溶性Lu/B-CAM在培养基中，并在荷HuH-7肝细胞癌（HCC）细胞的小鼠和HCC患者的血浆中。两种HCC细胞系HepG 2和HuH-7将Lu/B-CAM释放到培养基中。在HuH-7细胞中，Lu/B-CAM被MT 1-MMP切割，而HepG 2细胞则以MMP非依赖性方式释放Lu/B-CAM。释放到小鼠血浆中的Lu/B-CAM浓度与肿瘤大小相关。肝癌患者手术切除肿瘤后血浆中可溶性Lu/B-CAM明显降低。免疫组化结果显示，尽管Lu/B-CAM在大多数HCC中表达，但MT 1-MMP在肿瘤组织中并不总是表达，提示HCC患者血浆中也有部分Lu/B-CAM以MMP非依赖性方式释放。体外研究表明，从HCC细胞释放的可溶性Lu/B-CAM与LM-511结合。此外，可溶性Lu/B-CAM影响LM-511上的细胞迁移。这些结果表明，可溶性Lu/B-CAM不仅是HCC的新标志物，而且是肿瘤进展的调节剂。(C)2014爱思唯尔公司All rights reserved.
Lutheran (Lu), an immunoglobulin superfamily transmembrane receptor, is also known as basal cell adhesion molecule (B-CAM). Lu/B-CAM is a specific receptor for laminin alpha 5, a subunit of laminin-511 (LM-511) that is a major component of basement membranes in various tissues. Our previous study showed that Lu/B-CAM was cleaved by MT1-MMP and released from cell surfaces. In this study we examined the soluble Lu/B-CAM in culture media and in plasma of mice bearing HuH-7 hepatocellular carcinoma (HCC) cells and patients with HCC. Two HCC cell lines, HepG2 and HuH-7, released Lu/B-CAM into the culture media. Although Lu/B-CAM was cleaved by MT1-MMP in HuH-7 cells, HepG2 cells released Lu/B-CAM in a MMP-independent manner. The concentration of Lu/B-CAM released into mouse plasma correlated with tumor size. Moreover the soluble Lu/B-CAM in plasma of HCC patients was significantly decreased after resection of the tumor. Immunohistochemical studies showed that although the expression of Lu/B-CAM was observed in most HCCs, MT1-MMP was not always expressed in tumor tissues, suggesting that a part of Lu/B-CAM in plasma of HCC patients was also released in a MMP-independent manner. In vitro studies showed that the soluble Lu/B-CAM released from HCC cells bound to LM-511. Moreover the soluble Lu/B-CAM influenced cell migration on LM-511. These results suggest that soluble Lu/B-CAM serves as not only a novel marker for HCC but also a modulator in tumor progression. (C) 2014 Elsevier Inc. All rights reserved.