SURFACE HSC7010C10 CONFERS A GROWTH AND SURVIVAL ADVANTAGE TO OVAL CELLS, CHOLA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 原发性肝癌是全球癌症相关死亡的主要原因之一。我们的实验室研究肝祖细胞（啮齿动物的卵圆细胞）在肝癌发生中的作用。这些祖细胞位于肝胆管树的小管内，并与肝修复、再生和癌变有关。我们以前开发了一种表面反应性单克隆抗体，单克隆抗体OC.10，它识别胎儿肝导管细胞，肝祖细胞，成熟胆管细胞（胆管细胞）和肝细胞癌（HCC）共享的表位。初步数据表明，单克隆抗体OC. 10识别在这些细胞的细胞表面表达的Hsc 70的构象特异性表位，其促进体外增殖和存活以及体内胆管的形态发生。在这里，我们将研究的假设，单克隆抗体OC. 10激活信号通路，刺激细胞生长，防止细胞死亡，加速细胞成熟，活动所必需的适当的组织和维护。该提案中提出的一种可能性是MAb OC.10模拟与表面Hsc 70/OC.10相互作用的天然配体，以调节对生长和存活至关重要的信号传导途径。表面Hsc 70/OC.10和/或其天然配体的失调可能有助于祖细胞衍生的肝癌（包括HCC和源自成熟胆管细胞的胆管癌）的发展和进展。目的1使用卵圆细胞祖细胞系CDE 6、成熟胆管上皮（BDE）细胞和大鼠HCC系H5 D检查MAb OC.10对生长和存活的体外作用。目的2检测单克隆抗体OC.10对新生大鼠肝脏发育中胆管存活和增殖的体内影响。这些研究旨在进一步了解表面Hsc 70/OC. 10在肝脏发育和肝癌发生中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary liver cancer is one of the leading causes of cancer-related death worldwide. Our laboratory studies the role of hepatic progenitor cells (oval cells in rodents) in liver carcinogenesis. These progenitor cells are located within the ductules of the hepatic biliary tree and have been implicated in liver repair, regeneration and carcinogenesis. We previously developed a surface reactive monoclonal antibody, MAb OC.10, which recognizes an epitope shared by fetal liver ductal cells, hepatic progenitor cells, mature bile duct cells (cholangiocytes) and hepatocellular carcinomas (HCC). Preliminary data suggests that MAb OC.10 recognizes a conformation specific epitope of Hsc70 expressed at the cell surface of these cells that promotes proliferation and survival in vitro and morphogenesis of bile ducts in vivo. Here we will examine the hypothesis that MAb OC.10 activates signaling pathways that stimulates cell growth, prevents cell death and accelerates cellular maturation, activities essential for proper tissue organization and maintenance. A possibility presented in this proposal is that MAb OC.10 mimics a natural ligand that interacts with surface Hsc70/OC.10 to regulate signaling pathways critical to growth and survival. Dysregulation of surface Hsc70/OC.10 and/or its natural ligands could contribute to the development and progression of progenitor-derived liver cancers including HCC and cholangiocarcinomas originating from mature bile duct cells. Aim 1 examines the in vitro effect of MAb OC.10 on growth and survival using the oval cell progenitor cell line CDE6, mature bile duct epithlial (BDE) cells, and the rat HCC line, H5D. Aim 2 examines the in vivo effect of MAb OC.10 on survival and proliferation of developing bile ducts in newborn rat liver. These studies are intended to further our understanding of the role of surface Hsc70/OC.10 during liver development and hepatocarcinogenesis.