THROMBOSPONDIN 1 PREVENTS BREAST CANCER METASTASIS

血小板反应蛋白 1 预防乳腺癌转移

• 批准号: 6377724
• 负责人: KAREN O YEE
• 金额: $ 4.02万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-27 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6377724
• 关键词: MCF7 cell; RNase protection assay; antisense nucleic acid; breast neoplasms; collagen; enzyme linked immunosorbent assay; epithelium; female; metalloendopeptidases; metastasis; neoplasm /cancer invasiveness; thrombospondins; tissue inhibitor of metalloproteinases; transforming growth factors; tumor suppressor proteins; western blottings

Presently, effective therapies for breast cancer is compromised when cancer cells metastasize to other sites. One extracellular matrix protein, thrombospondin-1 (TSP1) has been shown to inhibit breast cancer metastasis in nude mice. At this time, it is not well understood how TSP1 prevents metastasis. In endothelial cells, TSP1 activates transforming growth factor beta (TGF-beta). TSP1 through TGF-beta could affect the levels and activation of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), enzymes that modulate the cells' ability to degrade extracellular matrices. The goal of this project is to characterize the relationship between TSP1, TGF-beta, MMPs and TIMPs in breast carcinoma cells to determine whether this pathway could be responsible for TSP1 inhibition of metastasis in vivo. The following questions will be addressed: 1. Does TSP1 activate TGF-beta in breast carcinoma cells? 2. Does TGF-beta affect the activation levels of MMP-2 and 9 and expression levels of TIMP-1 and 2 in breast carcinoma cells? 3. Does the levels of TSP1, TGF-beta, MMPs and TIMPs affect the ability of breast carcinoma cells to invade an extracellular matrix in vitro?

目前，当癌细胞转移到其他部位时，乳腺癌的有效治疗就会受到影响。 一种细胞外基质蛋白血小板反应蛋白-1 (TSP1) 已被证明可以抑制裸鼠中的乳腺癌转移。 目前，TSP1如何预防转移尚不清楚。 在内皮细胞中，TSP1 激活转化生长因子 β (TGF-β)。 TSP1 通过 TGF-β 可以影响基质金属蛋白酶 (MMP) 和基质金属蛋白酶组织抑制剂 (TIMP) 的水平和活化，这些酶调节细胞降解细胞外基质的能力。 该项目的目标是表征乳腺癌细胞中 TSP1、TGF-β、MMP 和 TIMP 之间的关系，以确定该通路是否可能与 TSP1 抑制体内转移有关。将解决以下问题： 1. TSP1 是否激活乳腺癌细胞中的 TGF-β？ 2. TGF-β是否影响乳腺癌细胞中MMP-2和9的激活水平以及TIMP-1和2的表达水平？ 3. TSP1、TGF-β、MMPs和TIMPs的水平是否影响乳腺癌细胞体外侵袭细胞外基质的能力？