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

整合素α_v、β_3仅在少数细胞类型中表达，如某些肿瘤细胞和破骨细胞。乳腺癌的特点是以骨吸收为主的多发性骨转移。只有破骨细胞才能吸收骨基质，而破骨细胞的激活对于骨转移的建立是必不可少的。在本研究中，我们检测了α_v、β_3在乳腺癌细胞中的表达与骨转移的关系。免疫组织化学显示α_vβ_3在两种人乳腺癌细胞系中均呈高表达，而在MKL-4中未见表达。流式细胞仪检测结果相似(α_vβ_3在MDA231和MDAMB435细胞中分别为82%、92%和26%)。在有骨转移的乳腺癌组织中，α_vβ_3高表达的发生率为58%(11/19)，而在无骨转移的乳腺癌组织中为39%(7/18)。有趣的是，α_v、β_3的阻断可防止体内的骨转移。在我们的裸鼠模型中，ECS处理组(20ug/kg/min)的骨转移灶数目为1.1±1.3个/只，而对照组为4.0±0个/只。而对照组的骨转移面积为2.8±1.6 mm^2，而ECS组的骨转移面积为0.6±1.2 mm^2。整合素α_v、β_3可作为乳腺癌骨转移的治疗靶点。

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.