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

SURFACE HSC7010C10 赋予椭圆形细胞生长和生存优势，CHOLA

• 批准号: 7725165
• 负责人: DAVID MILLS
• 金额: $ 3.11万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725165
• 关键词: Cancer Etiology; Cell Death; Cell Line; Cell surface; Cells; Cessation of life; Cholangiocarcinoma; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Ductal Epithelial Cell; Epitopes; Fetal Liver; Funding; Grant; Growth; Hepatic; Hepatocarcinogenesis; In Vitro; Institution; Laboratory Study; Ligands; Liver; Maintenance; Malignant neoplasm of liver; Molecular Conformation; Monoclonal Antibodies; Morphogenesis; Natural regeneration; Newborn Infant; Primary carcinoma of the liver cells; Rattus; Research; Research Personnel; Resources; Rodent; Role; Signal Pathway; Source; Stem cells; Surface; Tissues; United States National Institutes of Health; bile duct; biliary tract; carcinogenesis; cell growth; cholangiocyte; in vivo; oval cell; prevent; progenitor; repaired

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 原发性肝癌是全球与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（啮齿动物中椭圆形细胞）在肝癌发生中的作用。这些祖细胞位于肝胆道的管道内，与肝修复，再生和致癌作用有关。我们以前开发了一种表面反应性单克隆抗体MAB OC.10，该抗体识别由胎儿肝导管细胞，肝祖细胞，成熟的胆管细胞（胆管菌细胞）和肝细胞癌（HCC）共享的表位。初步数据表明，MAB OC.10识别在这些细胞的细胞表面表达的HSC70的特定构象表位，该表面在体外促进了体外体外的增殖和生存和形态发生。在这里，我们将研究以下假设：MAB OC.10激活刺激细胞生长，防止细胞死亡并加速细胞成熟的信号通路，这对于适当的组织组织和维持至关重要。该提案中提出的一种可能性是mab oc.10模拟自然配体与表面HSC70/OC.10相互作用以调节对生长和生存至关重要的信号通路。表面HSC70/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的发育和进展，包括HCC和胆管癌源自成熟的胆管细胞。 AIM 1使用椭圆形细胞祖细胞系CDE6，成熟的胆管上皮（BDE）细胞（BDE）细胞和大鼠HCC系H5D检查了MAB OC.10对生长和存活的体外影响。 AIM 2检查了MAB OC.10对新生大鼠肝脏中发育胆管生存和增殖的体内影响。这些研究旨在进一步了解我们对肝发育和肝癌发生过程中表面HSC70/OC.10的作用的理解。