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Study on the role of integrin alpha4beta1 in bone metastasis

整合素α4β1在骨转移中的作用研究

基本信息

批准号：
06670239
负责人：
MATSUURA Nariaki
金额：
$ 1.28万
依托单位：
Osaka University (1995)Wakayama Medical University (1994)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670239/
关键词：
Bone metastasis Integrin VCAM-1

项目摘要

1.Transfection of integrin alpha4beta1 cDNA to the cell : cDNA for integrin alpha4 (or alpha4 and beta1 both) was transfected into Chinese hamster ovary (CHO) cell. The expression of integrin alpha4beta1 on the transfected cell surface was confirmed by flow cytometry and immunoprecipitation.2.Biological analysis of the transfectant : Adhesion assay to VCAM-1 or fbronectin CS-1 peptide was examined in the transfected CHO cell (alpha4-CHO). As a result, alpha4-CHO cell was adhered both to VCAM-1 and CS-1 sufficiently.3.Metastasis experiment : alpha4-CHO or parent CHO cells were inoculated into nude mice. Only lung metastasis was observed in the nude mice in which CHO cells were inoculated, while bone metastasis was seen as well as lung metastasis in the nude mice in which alpha4-CHO cells were injected. Histological examination showed the proliferation of alpha4-CHO cells in the bone marrow and the invasion outside the bone in some cases. Clusters of tumor cells were sometimes found in the bone marrow, suggesting that bone marrow is the first emtastasis site. Bone metastasis was inhibited by the combination of anti-VCAM-1 and anti-alpha4 subunit. Since stroma cells in the bone marrow express VCAM-1 constitutively on the cell surface, alpha4-CHO cells might be adhered to the stroma cells and proliferated in the bone marrow. The tumor cells expressing integrin alpha4beta1 are supposed to metastasize to bone clinically, and the inhibition of metastasis will be expected by using neutralizing substances against integrin alpha4beta1 in the future.

1.细胞转染整合素alpha4beta1 cDNA：将整合素alpha4（或同时转染alpha4和beta1） cDNA转染中国仓鼠卵巢（CHO）细胞。流式细胞术和免疫沉淀法证实了整合素alpha4beta1在转染细胞表面的表达。转染物的生物学分析：在转染的CHO细胞（alpha4-CHO）中检测与VCAM-1或连接蛋白CS-1肽的粘附试验。结果表明，alpha4-CHO细胞与VCAM-1和CS-1均有充分的粘附。转移实验：将α 4-CHO或亲本CHO细胞接种于裸鼠。接种CHO细胞的裸鼠只观察到肺转移，而注射α 4-CHO细胞的裸鼠则观察到骨转移和肺转移。组织学检查显示骨髓内α - 4- cho细胞增生，部分患者骨外浸润。有时在骨髓中发现肿瘤细胞簇，提示骨髓是第一个转移部位。抗vcam -1和抗α - 4亚基联合作用可抑制骨转移。由于骨髓基质细胞在细胞表面组成性地表达VCAM-1，因此α - 4- cho细胞可能粘附于基质细胞并在骨髓中增殖。临床上认为表达整合素alpha4beta1的肿瘤细胞有骨转移的可能，未来有望利用整合素alpha4beta1的中和物质抑制转移。