INV OF ASTROCYTE CASPASE ACTV & CD40/CD40L SIGNALING INTERACTIONS IN ALZHEIMER?S

星形胶质细胞天冬氨酸蛋白酶活性的 INV

• 批准号: 7381316
• 负责人: TROY T ROHN
• 金额: $ 8.42万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381316
• 关键词: INV; ASTROCYTE; CASPASE; ACTV; CD40

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. Oncostatin M induces VEGF in human breast carcinoma cells: stimulation of angiogenesis in vitro and in vivo. Oncostatin M is a pleiotropic cytokine produced by many cell types, including neutrophils and tumor-associated mascrophages. OSM inhibits proliferation of breast cancer cells, and for this reason is being examined for its potential use in cancer treatment. Preliminary results from our lab show that OSM may promote pro-angiogenic factors in tumor cells. Additional studies show that OSM is expressed by tumor-associated neutrophils and breast cancer epithelial cells, but not by normal breast cancer tissue. Our data indicate that OSM stimulates breast cancer cells to produce angiogenesis-related matrix metalloproteinases (MMPs) and vascular endothelial growth factor-A (VEGF), which is an extremely potent angiogenic factor. Our goal is to understand the implications of VEGF induction to correctly evaluate the potential of OSM as a clinical cancer treatment. We hypothesize that VEGF produced by OSM-treated breast cancer cells will stimulate angiogenesis in vitro and in vivo. Our specific aims include: 1) To determine the OSM receptor and signaling pathway utilized to induce VEGF; 2) To demonstrate that VEGF produced by OSM-treated breast cancer cells will induce an angiogenic phenotype in cultured endothelial cells; and 3) To investigate the ability of OSM-induced VEGF to stimulate angiogenesis and promote the progression of breast carcinoma in vivo.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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代表。列出的机构适用于该中心，这不一定是调查员的机构。 OnCostatin M在人类乳腺癌细胞中诱导VEGF：体外和体内血管生成的刺激。 Oncostatin M是一种由许多细胞类型产生的多效细胞因子，包括中性粒细胞和与肿瘤相关的大共章。 OSM抑制乳腺癌细胞的增殖，因此正在检查其在癌症治疗中的潜在使用。我们实验室的初步结果表明，OSM可能促进肿瘤细胞中的促血管生成因子。其他研究表明，OSM是由肿瘤相关的嗜中性粒细胞和乳腺癌上皮细胞表达的，但不是由正常的乳腺癌组织表达。我们的数据表明，OSM刺激乳腺癌细胞产生与血管生成有关的基质金属蛋白酶（MMP）和血管内皮生长因子-A（VEGF），这是极有效的血管生成因子。我们的目标是了解VEGF诱导对正确评估OSM作为临床癌症治疗的潜力的含义。 我们假设由OSM处理的乳腺癌细胞产生的VEGF会在体外和体内刺激血管生成。我们的具体目的包括：1）确定用于诱导VEGF的OSM受体和信号通路； 2）证明由OSM处理的乳腺癌细胞产生的VEGF将诱导培养的内皮细胞中的血管生成表型； 3）研究OSM诱导的VEGF刺激血管生成并促进体内乳腺癌的进展的能力。