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

Application of integrin α4β1 for diagnosis and therapy of bone metastasis

整合素α4β1在骨转移诊治中的应用

基本信息

批准号：
10670158
负责人：
MATSUURA Nariaki
金额：
$ 2.43万
依托单位：
Osaka 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-10670158/
关键词：
bone metastasis chemotherapy integrin α4β1 transfection インテグリン細胞運動 VCAM-1 骨髄破骨細胞

项目摘要

In the previous study α4-CHO cell, transfectant of integrin α4β1 for Chinese hamster ovary cell, caused prominent bone metastasis in vivo and the interaction of α4β1 and *CAM-1 (vascular cell adhesion molecule-1) was important for the mechanism of bone metastasis in this model.α4-CHO cell was used as a model of bone metastasis of hormone receptor negative breast cancer and the effect of UFT and medroxyprogesterone acetate (MPA) administration was examined. The degree of bone metastases was observed for the inhibitory effect of those drugs for bone metastasis. The adverse effect of drugs was evaluated for the diet volume and body weight changes. The drugs were administered orally every day and mice were sacrificed to examine metastasis. As a result, administration of middle dose of UFT (20mg/kg/day) or high dosage of UFT (30mg/kg/day) in combination with MPA suppressed bone metastasis. Administration of high dose of UFT in combination with MPA resulted in the suppression of adverse effects of UFT such as increased food intake, decreased body weight loss, and reduced necrotic change of liver. Therefore combination therapy of UFT and MPA would be useful for bone metastasis both in potentiation of effects and alleviation of *de effects.Expression of mRNA (R-PCR) and protein (imuunohistochemistry) of integrin α4β1 was investigated in the primary and metastatic lesions of bone metastasis of breast cancer, prostate cancer and lung cancer. As a result, overexpression of α4β1 in the metastatic lesion was observed, while there was no difference of the α3β1 expression between primary and metastatic lesions. These data suggested α4β1 might play some roles in bone metastasis.

在前期的研究中，以整合素α4β1转染中国仓鼠卵巢细胞，在体内引起显著的骨转移和α4β1和 *CAM-1的相互作用结论：α4-β 1在骨转移中起重要作用，α4-β 1在骨转移中起重要作用。以CHO细胞作为激素受体阴性乳腺癌骨转移模型，观察UFT和醋酸甲羟孕酮（MPA）对骨转移的影响管理进行了检查。观察骨转移的程度，观察药物对骨转移的抑制作用。通过观察饮食量和体重的变化来评价药物的不良反应。每天口服给药，处死小鼠以检查转移。结果表明，中剂量UFT（20 mg/kg/d）或高剂量UFT（30 mg/kg/d）联合MPA对骨转移有抑制作用。大剂量UFT与MPA联合给药可抑制UFT的不良反应，如摄食量增加、体重减轻和肝脏坏死变化减少。本研究应用逆转录聚合酶链反应（R-PCR）和免疫组化（免疫组化）方法检测了乳腺癌、前列腺癌和肺癌骨转移灶中整合素α4β1（integrin α4β1）的mRNA和蛋白表达。结果表明，α4β1在转移灶中呈高表达，而α3β1在原发灶和转移灶中的表达无明显差异。提示α4β1可能在骨转移中起一定作用。