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目的研究整合素αvβ3在乳腺癌骨髓微转移中的作用。方法流式细胞仪检测乳腺癌细胞株MCF7、MDA-MB-231、MDA-MB-435s中整合素αvβ3的表达,细胞黏附、迁移试验及共聚焦显微镜检测整合素αvβ3功能,实时荧光定量RT-PCR检测抗整合素αvβ3抗体LM609对裸鼠乳腺癌骨髓微转移模型的影响。结果 MCF-7细胞膜上整合素αvβ3受体为阴性,MDA-MB-231、MDA- MB-435s细胞膜上整合素αvβ3受体为阳性。用LM609封闭αvβ3受体后,αvβ3受体阳性细胞对细胞外基质蛋白中玻璃体结合蛋白的黏附和迁移能力显著减弱。以αvβ3受体阳性细胞制作的裸鼠乳腺癌骨髓微转移模型中,经LM609处理后,可显著减少乳腺癌骨髓微转移的肿瘤细胞(P<0.05)。结论整合素αvβ3受体过度表达增强乳腺癌细胞黏附和迁移能力,从而促进肿瘤细胞的骨髓微转移,而以Lm609封闭αvβ3受体可抑制上述作用。
Objective To investigate the role of integrin αvβ3 in bone marrow micrometastasis in breast cancer. Methods The expression of integrin αvβ3 in breast cancer cell lines MCF7, MDA-MB-231 and MDA-MB-435s was detected by flow cytometry. The function of integrin αvβ3 and cell adhesion, migration and confocal microscopy were detected by real- Effect of anti - integrin αvβ3 antibody LM609 on bone marrow micrometastasis in nude mice. Results The integrin αvβ3 receptor of MCF-7 cells was negative, and the integrin αvβ3 receptor was positive on the cell membrane of MDA-MB-231 and MDA-MB-435s. After the αvβ3 receptor was blocked with LM609, the ability of αvβ3 receptor positive cells to adhere and migrate to vitronectin in extracellular matrix proteins was significantly weakened. In the model of bone marrow micrometastasis in nude mice with αvβ3-positive cells, the treatment of LM609 could significantly reduce the metastasis of breast cancer cells (P <0.05). Conclusion The overexpression of integrin αvβ3 enhances the adhesion and migration of breast cancer cells, which can promote the bone marrow micrometastasis of tumor cells. However, blocking the αvβ3 receptor with Lm609 can inhibit the above effects.