Novel function for VEGF in breast carcinoma survival

VEGF 在乳腺癌生存中的新功能

• 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
• 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; 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

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）通过促进血管生成有助于乳腺癌进展。 当前的研究介绍了VEGF在促进乳腺癌细胞侵袭和迁移方面的新功能。 具体而言，该提案解决了以下假设：乳腺癌细胞的VEGF分泌通过与同一或邻近肿瘤细胞上的VEGF受体结合来促进其侵袭。 此外，假设这种VEGF自分泌信号传导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。 使用反义策略，将探索抑制VEGF表达对体外乳腺癌细胞侵袭和迁移的影响。 此外，将探索这种假设，即这种自分泌信号传导通过在这些细胞中维持构成升高的PI3-激酶活性来驱动乳腺癌的侵袭和迁移。 最后，将检查VEGF受体神经蛋白在该VEGF自分泌功能中的作用。 具体而言，将研究抑制内源性神经蛋白功能对乳腺癌侵袭和迁移的抑制性抗体的影响以及缺失构建体。 最后，我将评估乳腺癌细胞中VEGF自分泌信号传导对免疫缺陷小鼠的生长和转移的影响。 这种新型VEGF功能的表征对于扩大我们对乳腺癌进展的多个步骤的了解至关重要。