Role of laminin alpha5 and its receptors in fibrotic liver and hepatocellular carcinoma

层粘连蛋白α5及其受体在纤维化肝和肝细胞癌中的作用

基本信息

批准号：
17590307
负责人：
KIKKAWA Yamato
金额：
$ 2.6万
依托单位：
Tokyo University of Pharmacy and Life Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590307/
关键词：
extarcellular matrix laminin integrin lutheran hepatocellular carcinoma fibrotic liver liver

项目摘要

Laminins are a diverse group of alpha/beta/gamma heterotrimers formed from five alpha, three beta and three gamma chains ; they are major components of all basal laminae (BLs). One laminin chain that has garnered particular interest due to its widespread expression pattern and importance during development is laminin alpha5. Little is known, however, about the expression and function of laminins containing the alpha5 chain in human hepatocellular carcinoma (HCC). Here, using a specific antibody, we examined the expression of laminin alpha5 in normal liver and in HCCs. In normal liver, although laminin alpha5 was observed in hepatic BLs underlying blood vessels and bile ducts, it was absent from the parenchyma, which may be the origin of HCC. On the other hand, laminin alpha5 deposition was observed throughout all HCCs tested, regardless of tumor grade. In well differentiated HCCs, it localized along the trabecules of the tumor. In poorly-differentiated HCCs, it was present in surrounding tumor nodules. In HCC cell lines, laminin alpha5 heterotrimerized with beta and gamma chains and was secreted into the culture media. To attempt to understand the function of laminins containing alpha5, the expression of its receptors in HCCs was also determined. In this regard, alpha3betal/alpha6betal integrins and Lutheran/basal cell adhesion molecule (Lu/B-CAM) were expressed in HCC cells. In vitro studies showed that HCC cells readily attached to laminin containing the alpha5 chain, more so than did primary hepatocytes. In addition to alpha3betal/alpha6betal integrins and Lu/B-CAM, laminin alpha5 was recognized by integrin alphalbetal, which also was expressed in HCC cells. These results suggest that laminins containing alpha5 serve as functional substrates regulating progression of HCC.

层粘连蛋白是由五个 α、三个 β 和三个 γ 链形成的多种 α/β/γ 异三聚体；它们是所有基底层 (BL) 的主要组成部分。层粘连蛋白 α5 是一种层粘连蛋白链，因其广泛的表达模式和在发育过程中的重要性而受到特别关注。然而，关于含有 α5 链的层粘连蛋白在人肝细胞癌 (HCC) 中的表达和功能知之甚少。在这里，我们使用特异性抗体检查了正常肝脏和 HCC 中层粘连蛋白 α5 的表达。在正常肝脏中，虽然在血管和胆管下方的肝BL中观察到了层粘连蛋白α5，但实质上却没有层粘连蛋白α5，这可能是HCC的起源。另一方面，无论肿瘤等级如何，在所有测试的 HCC 中都观察到层粘连蛋白 α5 沉积。在分化良好的 HCC 中，它沿着肿瘤的小梁定位。在低分化的 HCC 中，它存在于周围的肿瘤结节中。在 HCC 细胞系中，层粘连蛋白 α5 与 β 链和 γ 链异三聚化并分泌到培养基中。为了尝试了解含有 alpha5 的层粘连蛋白的功能，还测定了其受体在 HCC 中的表达。在这方面，α3β1/α6β1整合素和路德/基底细胞粘附分子(Lu/B-CAM)在HCC细胞中表达。体外研究表明，HCC 细胞比原代肝细胞更容易附着于含有 α5 链的层粘连蛋白。除了 α3β1/α6β1 整合素和 Lu/B-CAM 之外，层粘连蛋白 α5 也被整合素 α1β1 识别，整合素 α1β1 也在 HCC 细胞中表达。这些结果表明含有 α5 的层粘连蛋白可作为调节 HCC 进展的功能底物。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The LG1-3 tandem of laminin alphas harbors the binding sites of Luther an/basal cell adhesion molecule and alpha3betal/alpha6betal integrins

层粘连蛋白 α 的 LG1-3 串联包含 Luther an/基底细胞粘附分子和 alpha3beta/alpha6beta 整联蛋白的结合位点

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Yamato Kikkawa
通讯作者：
Yamato Kikkawa

Integrin-dependent cell behavior on ECM peptide-conjugated chitosan membranes

ECM 肽缀合壳聚糖膜上的整合素依赖性细胞行为

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Mochizuki; M.; Yamagata; N.; Philp; D.; Hozumi; K.; Watanabe; T.; Kikkawa. Y.; Kadoya; Y.; Kleinman; H. K.; Nomizu; M
通讯作者：
M

The LG1-3 tandem of laminin alpha5 harbors the binding sites of Lutheran/basal cell adhesion molecule and alpha3betal/alpha6betal integrins

层粘连蛋白 α5 的 LG1-3 串联包含路德/基底细胞粘附分子和 alpha3beta/alpha6beta 整联蛋白的结合位点