ONCOSTATIN M INDUCES VEGF IN HUMAN BREAST CARCINOMA CELLS

制瘤素 M 在人乳腺癌细胞中诱导 VEGF

• 批准号: 7381315
• 负责人: CHERYL LYNN JORCYK
• 金额: $ 7.48万
• 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/7381315
• 关键词: ONCOSTATIN; INDUCES; VEGF; HUMAN; BREAST

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 macrophages. 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。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。抑瘤素M诱导人乳腺癌细胞中的VEGF：在体外和体内刺激血管生成。 抑瘤素M是由许多细胞类型产生的多效性细胞因子，包括嗜中性粒细胞和肿瘤相关巨噬细胞。OSM抑制乳腺癌细胞的增殖，因此正在研究其在癌症治疗中的潜在用途。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由肿瘤相关中性粒细胞和乳腺癌上皮细胞表达，但不被正常乳腺癌组织表达。我们的数据表明，OSM刺激乳腺癌细胞产生血管生成相关的基质金属蛋白酶（MMPs）和血管内皮生长因子-A（VEGF），这是一种非常有效的血管生成因子。我们的目标是了解VEGF诱导的意义，以正确评估OSM作为临床癌症治疗的潜力。 我们假设，OSM处理的乳腺癌细胞产生的VEGF将刺激血管生成在体外和体内。我们的具体目标包括：1）确定用于诱导VEGF的OSM受体和信号传导途径; 2）证明由OSM处理的乳腺癌细胞产生的VEGF将在培养的内皮细胞中诱导血管生成表型;和3）研究OSM诱导的VEGF刺激血管生成和促进体内乳腺癌进展的能力。