权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The relationship between the expression of the integrin alpha v beta 3 in breast cancer cells and bone metastasis

乳腺癌细胞整合素αvβ3表达与骨转移的关系

基本信息

批准号：
10671134
负责人：
IKEDA Tadashi
金额：
$ 2.05万
依托单位：
KEIO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671134/
关键词：
human breast cancer bone metastasis Integrin α_vβ_3 Flowcytometry nude rat model echistatin RGD tripeptide RT-PCR インテブリンα_Vβ_3 乳癌骨転移接着因子インデブリンαvβ3 インテグリンαvβ3

项目摘要

Integrin α_vβ_3 is expressed only in limited number of cell types such as some tumor cells and osteoclast. Breast cancer is characterized by frequent bone metastasis with dominant bone resorption. Only osteoclast is capable to resorb bone matrix and activation of osteoclast is essential for establishment of bone metastasis. In present study, we examined the expression of α_vβ_3 in breast cancer cells as to bone metastasis. Over-expression of α_vβ_3 was shown in both human breast cancer cell lines : MDA-MB-231 and MDA-MB-435, but not in MKL-4 with immunohistochemical study. Flowcytometry study showed the similar results (α_vβ_3 was detected in 82%, 92% of MDA-MB-231 and MDA-MB-435 cells, respectively, and 26% of MKL-4). Using breast cancer tissues, over-expression of α_vβ_3 was recognized 58% of patients (11/19) with bone metastasis while 39% of patients (7/18) without bone metastasis. Interestingly, the blockade of α_vβ_3 with echistatin (RGD tripeptide) prevented from metastasizing to bone in vivo. In our nude rat model, echistatin treatment (20 ug/kg/min) animals demonstrated bone metastasis 1.1±1.3 sites/rat, compared to control animals 4.0±0 sites/rat. Also the area of bone metastasis in animals with echistatin treatment was 0.6±1.2 mm^2 compared to 2.8±1.6 mm^2 with control animals. Integrin α_vβ_3 as therapeutic targets in bone metastasis of breast cancer has been suggested.

整合素α_vβ_3仅在部分肿瘤细胞和破骨细胞中表达。乳腺癌的特点是骨转移频繁，以骨吸收为主。只有破骨细胞才能吸收骨基质，而破骨细胞的激活是骨转移的必要条件。本研究探讨了α_vβ_3在乳腺癌细胞中的表达与骨转移的关系。α_vβ_3在人乳腺癌细胞系MDA-MB-231和MDA-MB-435中均有过表达，而在MKL-4中无过表达。流式细胞术检测结果相似（α_v - β_3在MDA-MB-231和MDA-MB-435细胞中分别检测到82%、92%，MKL-4细胞中检测到26%）。在乳腺癌组织中，有骨转移的患者中有58%（11/19）检测到α_vβ_3过表达，无骨转移的患者中有39%（7/18）检测到α_vβ_3过表达。有趣的是，用echistatin （RGD三肽）阻断α_vβ_3可以在体内阻止骨转移。在我们的裸鼠模型中，给药（20 ug/kg/min）的动物出现骨转移1.1±1.3个位点/大鼠，而对照组动物为4.0±0个位点/大鼠。此外，接受echistatin治疗的动物骨转移面积为0.6±1.2 mm^2，而对照组为2.8±1.6 mm^2。整合素α_vβ_3可能是乳腺癌骨转移的治疗靶点。