Novel function for VEGF in breast carcinoma survival

VEGF 在乳腺癌生存中的新功能

基本信息

批准号：
6640381
负责人：
ROBIN Elizabeth BACHELDER
金额：
$ 15.19万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-01 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6640381
关键词：
antisense nucleic acid athymic mouse autocrine blocking antibody breast neoplasms carcinoma cell line cell migration growth factor receptors metastasis neoplasm /cancer blood supply neoplasm /cancer invasiveness neoplastic process nerve /myelin protein phosphatidylinositol 3 kinase vascular endothelial growth factors

项目摘要

DESCRIPTION (provided by applicant): The vascular endothelial growth factor (VEGF) is known to contribute to breast carcinoma progression by promoting angiogenesis. The current studies address a novel function for VEGF in promoting the invasion and migration of breast carcinoma cells. Specifically, this proposal addresses the hypothesis that VEGF secretion by breast carcinoma cells promotes their invasion by binding to VEGF receptors on the same or neighboring tumor cells. Moreover, it is hypothesized that this VEGF autocrine signaling contributes to breast carcinoma invasion by promoting the PI3-kinase-dependent migration of these cells. Using an antisense strategy, the effects of inhibiting VEGF expression on the invasion and migration of breast carcinoma cells in vitro will be explored. Moreover, the hypothesis that this autocrine signaling drives breast carcinoma invasion and migration by maintaining constitutively elevated levels of PI3-kinase activity in these cells will be explored. Finally, a role for the VEGF receptor neuropilin in this VEGF autocrine function will be examined. Specifically, the effects of neuropilin inhibitory antibodies, as well as deletion constructs that inhibit endogenous neuropilin function on breast carcinoma invasion and migration will be investigated. Finally, I will assess the effects of specifically inhibiting VEGF autocrine signaling in breast carcinoma cells on their growth and metastasis in immunodeficient mice. The characterization of this novel VEGF function will be critical in broadening our knowledge of the multiple steps involved in breast carcinoma progression.

描述（由申请人提供）：已知血管内皮生长因子（VEGF）通过促进血管生成而促进乳腺癌进展。目前的研究探讨了 VEGF 在促进乳腺癌细胞侵袭和迁移方面的新功能。具体来说，该提案提出了这样的假设：乳腺癌细胞分泌的 VEGF 通过与相同或邻近肿瘤细胞上的 VEGF 受体结合来促进其侵袭。此外，据推测，这种 VEGF 自分泌信号通过促进这些细胞的 PI3 激酶依赖性迁移来促进乳腺癌侵袭。采用反义策略，探讨抑制VEGF表达对体外乳腺癌细胞侵袭和迁移的影响。此外，我们还将探讨以下假设：这种自分泌信号通过维持这些细胞中 PI3 激酶活性的持续升高水平来驱动乳腺癌侵袭和迁移。最后，将检查 VEGF 受体神经毡蛋白在 VEGF 自分泌功能中的作用。具体来说，将研究神经毡蛋白抑制性抗体以及抑制内源性神经毡蛋白功能的缺失构建体对乳腺癌侵袭和迁移的影响。最后，我将评估特异性抑制乳腺癌细胞中 VEGF 自分泌信号传导对其在免疫缺陷小鼠中生长和转移的影响。这种新的 VEGF 功能的表征对于拓宽我们对乳腺癌进展中涉及的多个步骤的认识至关重要。