Role of Osteopontin in Tumor Promotion

骨桥蛋白在肿瘤促进中的作用

• 批准号: 6621608
• 负责人: PI-LING CHANG
• 金额: $ 27.04万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-18 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621608
• 关键词: antisense nucleic acid; autocrine; chemical carcinogenesis; gene induction /repression; genetically modified animals; laboratory mouse; neoplasm /cancer genetics; osteopontin; phorbols; skin neoplasms

DESCRIPTION: (PROVIDED BY APPLICANT) Most initiated cells that contain genetic alterations by carcinogens can remain dormant and will not develop into tumors or progress to malignancies unless further internal or external factors, called tumor promoters, persistently stimulate these cells. Therefore, malignancies commonly develop much later in life. The mechanism of tumor promotion is not well understood. Identification of cellular and molecular participants involved in the promotion stage of carcinogenesis is a subject of importance as such information could provide the key to preventing certain malignancies. Our long-term goal is to understand how matrix proteins stimulated by tumor promoters participate in the process of tumorigenesis. Specifically, we will study the secreted, adhesive protein, osteopontin (OPN). OPN expression is elevated in several types of human cancers and premalignant tumors. Experimental evidences support the role of OPN as a mediator of tumor promotion. Thus, we hypothesize that OPN acts as an autocrine stimulus for tumor promotion of initiated cells. To test this hypothesis, we will use both in vitro and in vivo tumor promotion models. Specifically, we intend to determine the extent to which OPN induction is required for tumor promotion in JB6 cells, model for tumor promotion studies. We have developed unique genetic tools, antisense OPN JB6 clones and sense OPN JB6 clones, to determine OPN's effect on colony formation on soft agar and tumorigenicity in immunodeficient mice. We will evaluate the cellular and molecular mechanism(s) whereby OPN transforms JB6 cells. In addition, the importance of OPN in tumor promotion in vivo will be addressed by the lack of OPN expression and targeted expression of OPN in epidermis. Together, these studies will provide a better understanding of the role of OPN in tumor promotion and may contribute to the design of a mechanism-based strategy for cancer prevention.

描述：（由申请人提供）大多数起始细胞含有遗传基因 致癌物引起的改变可以保持休眠状态，不会发展成肿瘤 或进展为​​恶性肿瘤，除非有进一步的内部或外部因素，称为 肿瘤促进剂持续刺激这些细胞。因此，恶性肿瘤 通常在晚年才发展。肿瘤促进机制不 很好理解。识别涉及的细胞和分子参与者 在致癌的促进阶段本身就是一个重要的课题 信息可以提供预防某些恶性肿瘤的关键。我们的 长期目标是了解肿瘤如何刺激基质蛋白 启动子参与肿瘤发生过程。具体来说，我们将 研究分泌的粘附蛋白骨桥蛋白 (OPN)。 OPN 表达式为 在几种人类癌症和癌前肿瘤中升高。 实验证据支持 OPN 作为肿瘤介质的作用 晋升。因此，我们假设 OPN 作为自分泌刺激物 启动细胞的肿瘤促进。为了检验这个假设，我们将使用两者 体外和体内肿瘤促进模型。具体来说，我们打算 确定 OPN 诱导对于肿瘤促进所需的程度 JB6细胞，肿瘤促进研究的模型。我们开发了独特的基因 工具、反义 OPN JB6 克隆和正义 OPN JB6 克隆，以确定 OPN 对软琼脂上集落形成的影响和免疫缺陷的致瘤性 老鼠。我们将评估 OPN 的细胞和分子机制 转化 JB6 细胞。此外，OPN 在肿瘤促进中的重要性 体内将通过缺乏 OPN 表达和靶向表达来解决 OPN 位于表皮。总之，这些研究将提供更好的理解 OPN 在肿瘤促进中的作用，可能有助于设计 基于机制的癌症预防策略。