Iguchi H, Tanaka S, Ozawa Y, Kashiwakuma T, Kimura T, Hiraga T, Ozawa H, Kono A
Department of Biochemistry, National Kyushu Cancer Center, Fukuoka, Japan.
Cancer Res. 1996 Sep 1;56(17):4040-3.
In the formation of bone metastasis, osteoclastic bone resorption is necessary before the expansion of tumor cells from bone marrow to bone, and several cytokines, which possess osteoclast-stimulating activity, could be involved in this step. In this paper, we describe a bone metastasis model in nude mice using human lung squamous cell carcinoma-derived cells (HARA), in which the parathyroid hormone-related protein (PTHrP) gene, one of the most potent osteoclast-activating factors, is strongly expressed. The injection of HARA cells (1 x 10(5)) into the left cardiac ventricle resulted in tumor colonies exclusively in the skeletal system at 4 and/or 8 weeks after inoculation. An anti-PTHrP antibody injected via a tail vein reduced the incidence of bone metastases, number of tumor colonies, and tumor volume after the inoculation of HARA cells. The injection of another line of human lung squamous cell carcinoma-derived cells (QG-56), in which the PTHrP gene is not expressed, resulted in no bone metastasis. These findings suggest that PTHrP plays an important role in the formation of bone metastasis.
在骨转移的形成过程中，破骨细胞性骨吸收在肿瘤细胞从骨髓向骨扩展之前是必要的，几种具有破骨细胞刺激活性的细胞因子可能参与这一步骤。在本文中，我们描述了一种使用人肺鳞状细胞癌衍生细胞（HARA）建立的裸鼠骨转移模型，其中甲状旁腺激素相关蛋白（PTHrP）基因，一种最有效的破骨细胞激活因子，被强烈表达。将HARA细胞（1×10⁵）注入左心室，在接种后4周和/或8周，肿瘤集落仅出现在骨骼系统中。通过尾静脉注射抗PTHrP抗体可降低接种HARA细胞后的骨转移发生率、肿瘤集落数量和肿瘤体积。注射另一株不表达PTHrP基因的人肺鳞状细胞癌衍生细胞（QG - 56）则不会导致骨转移。这些发现表明PTHrP在骨转移的形成中起重要作用。
