Application of integrin α4β1 for diagnosis and therapy of bone metastasis

在先前的研究中，整合素α4β1转染中国仓鼠卵巢细胞α4-CHO细胞，在体内引起了显著的骨转移，α4β1与*CAM-1（血管细胞粘附分子-1）的相互作用是该模型骨转移的重要机制。以α4-CHO细胞为激素受体阴性乳腺癌骨转移模型，观察UFT和醋酸甲孕酮（MPA）对骨转移的影响。观察骨转移程度，观察药物对骨转移的抑制作用。评估药物对饮食量和体重变化的不良影响。每天口服药物，并处死小鼠观察转移情况。结果表明，中剂量UFT （20mg/kg/day）或高剂量UFT （30mg/kg/day）联合MPA可抑制骨转移。大剂量UFT联合MPA可抑制UFT的不良反应，如增加食物摄入量，减轻体重减轻，减少肝脏坏死变化。因此，UFT与MPA联合治疗对骨转移具有增强和减轻作用的作用。研究了整合素α4β1 mRNA （R-PCR）和蛋白（免疫组化）在乳腺癌、前列腺癌和肺癌骨转移原发灶和转移灶中的表达。可见α4β1在转移灶中过表达，而α3β1在原发灶和转移灶间表达无差异。提示α4β1可能在骨转移中起一定作用。

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.