Yan Wangjun, Xiao Jianru, Liu Tielong, Huang Wending, Yang Xinghai, Wu Zhipeng, Huang Quan, Qian Ming
Spine Tumor Center, Department of Orthopedics, Changzheng Hospital Affiliated the Second Military Medical University, No. 415 Fengyang Road, Shanghai, 200003, China.
Tumour Biol. 2013 Jun;34(3):1391-7. doi: 10.1007/s13277-012-0584-z. Epub 2013 Mar 1.
Previous studies have demonstrated that Hsp90 is closely associated with tumor metastases, and inhibition of Hsp90 expression can result in reduced tumor invasiveness and migration capability. However, its role in spinal metastases of breast carcinoma remains unknown. The paper aimed to further detect Hsp90 expression in a mouse model of spinal metastases of breast carcinoma which was established by left ventricular injection of breast cancer cell lines TM40D to nude mice. The BALB/c nude mice were divided into four groups at random: blank control group (n=10), model group (n=30), negative control group (n=10), and experimental group (n=30). Mice in the experimental group were given intraperitoneal injection of 12 mg/kg 17-allylamino-demethoxy geldanamycin (17-AAG), an inhibitor for Hsp90. The protein and mRNA expressions of Hsp90 were respectively determined using immunohistochemistry and real-time PCR. Bioluminescence imaging, dissection, and hematoxylin and eosin staining were performed to observe tumor formation and bone damage. Our results suggested that Hsp90 expression in mice with breast cancer metastasis in the spine was significantly higher than that in normal mice. Furthermore, Hsp90 expression was decreased and the spinal metastasis from breast cancer was inhibited by 17-AAG application. Hsp90 could be considered as an indicator to forecast tumor metastasis and provide a target for the treatment of spinal metastasis of breast cancer.
先前的研究表明,热休克蛋白90(Hsp90)与肿瘤转移密切相关,抑制Hsp90表达可导致肿瘤侵袭性和迁移能力降低。然而,其在乳腺癌脊柱转移中的作用尚不清楚。本文旨在进一步检测通过向裸鼠左心室注射乳腺癌细胞系TM40D建立的乳腺癌脊柱转移小鼠模型中Hsp90的表达。将BALB/c裸鼠随机分为四组:空白对照组(n = 10)、模型组(n = 30)、阴性对照组(n = 10)和实验组(n = 30)。实验组小鼠腹腔注射12 mg/kg的Hsp90抑制剂17-烯丙基氨基-去甲氧基格尔德霉素(17-AAG)。分别采用免疫组织化学和实时PCR检测Hsp90的蛋白和mRNA表达。进行生物发光成像、解剖及苏木精-伊红染色以观察肿瘤形成和骨损伤情况。我们的结果表明,脊柱发生乳腺癌转移的小鼠中Hsp90表达显著高于正常小鼠。此外,应用17-AAG可降低Hsp90表达并抑制乳腺癌的脊柱转移。Hsp90可被视为预测肿瘤转移的指标,并为乳腺癌脊柱转移的治疗提供靶点。