Department of Gynecology and Obstetrics, Georg-August-University, Robert-Koch-Street 40, 37075 Göttingen, Germany.
Breast Cancer Res Treat. 2011 Dec;130(3):783-90. doi: 10.1007/s10549-011-1358-9. Epub 2011 Jan 30.
Metastasis to bone is a frequent problem of advanced breast cancer. Particularly breast cancers, which do not express estrogen and progesterone receptors and which have no overexpression/amplification of the HER2-neu gene, so called triple-negative breast cancers, are considered as very aggressive and possess a bad prognosis. About 60% of all human breast cancers and about 74% of triple-negative breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a therapeutic target. Recently, we could show that bone-directed invasion of human breast cancer cells in vitro is time- and dose-dependently reduced by GnRH analogs. In the present study, we have analyzed whether GnRH analogs are able to reduce metastases of triple-negative breast cancers in vivo. In addition, we have evaluated the effects of GnRH analogs on tumor growth. To quantify formation of metastasis by triple-negative MDA-MB-435 and MDA-MB-231 human breast cancers, we used a real-time PCR method based on detection of human-specific alu sequences measuring accurately the amount of human tumor DNA in athymic mouse organs. To analyze tumor growth, the volumes of breast cancer xenotransplants into nude mice were measured. We could demonstrate that GnRH analogs significantly reduced metastasis formation by triple-negative breast cancer in vivo. In addition, we could show that GnRH analogs significantly inhibited the growth of breast cancer into nude mice. Side effects were not detectable. In conclusion, GnRH analogs seem to be suitable drugs for an efficacious therapy for triple-negative, GnRH receptor-positive human breast cancers to prevent metastasis formation.
转移到骨骼是晚期乳腺癌的常见问题。特别是那些不表达雌激素和孕激素受体，也没有 HER2-neu 基因过表达/扩增的乳腺癌，即所谓的三阴性乳腺癌，被认为具有很强的侵袭性和不良预后。大约 60%的所有人类乳腺癌和约 74%的三阴性乳腺癌表达促性腺激素释放激素（GnRH）受体，这可能被用作治疗靶点。最近，我们发现 GnRH 类似物可以在体外时间和剂量依赖性地减少人乳腺癌细胞的骨定向侵袭。在本研究中，我们分析了 GnRH 类似物是否能够减少三阴性乳腺癌的体内转移。此外，我们还评估了 GnRH 类似物对肿瘤生长的影响。为了定量分析三阴性 MDA-MB-435 和 MDA-MB-231 人乳腺癌的转移形成，我们使用了一种基于检测人类特异性 alu 序列的实时 PCR 方法，该方法可以准确测量无胸腺鼠器官中人类肿瘤 DNA 的量。为了分析肿瘤生长，我们测量了乳腺癌异种移植到裸鼠中的体积。我们发现 GnRH 类似物能够显著减少三阴性乳腺癌在体内的转移形成。此外，我们还发现 GnRH 类似物能够显著抑制裸鼠中乳腺癌的生长。没有检测到副作用。总之，GnRH 类似物似乎是治疗三阴性、GnRH 受体阳性人类乳腺癌以预防转移形成的有效药物。
