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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。抑癌素M在人乳腺癌细胞中诱导VEGF：体外和体内血管生成的刺激。抑癌素M是多种细胞类型产生的多效细胞因子，包括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在肿瘤相关的中性粒细胞和乳腺癌上皮细胞中表达，但在正常乳腺癌组织中不表达。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会刺激体外和体内血管生成。我们的具体目标包括：1)确定OSM受体和用于诱导VEGF的信号通路；2)证实经osm处理的乳腺癌细胞产生的VEGF在培养的内皮细胞中诱导血管生成表型；3)探讨osm诱导的VEGF在体内刺激血管生成、促进乳腺癌进展的能力。

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.