CeRMS (Center for Experimental Research and Medical Studies), Department of Medical Oncology, San Giovanni Battista Hospital, and Department of Surgical and Medical Discplines, University of Turin, Turin, Italy.
Oncol Rep. 2013 Apr;29(4):1453-8. doi: 10.3892/or.2013.2280. Epub 2013 Feb 6.
Gastric cancer is one of the most common and lethal malignancies worldwide. Bone metastases in gastric cancer are less common than in other solid tumors, but when they occur the prognosis is generally poor. Increased osteoclastogenesis and osteoclast activity are common features in bone metastases caused by different osteotropic cancer. We investigated osteoclastogenesis and its mechanisms in gastric cancer by enrolling 31 newly diagnosed gastric cancer patients and 45 healthy controls. We studied in vitro osteoclastogenesis in the peripheral blood mononuclear cell cultures of patients and controls, showing spontaneous osteoclastogenesis for half of the patients. This osteoclastogenesis was RANKL- and TNF-α-independent. We analyzed primary tumor and bone metastatic tissues of gastric cancer for the expression of genes involved in osteoclastogenesis. The expression of transforming growth factor-β (TGF-β), osteoprotegerin (OPG), IL-7 and dickkopf-1 (DKK-1) was higher in primary tumors than in bone metastases. RANKL was not detectable in primary tumor or in bone metastatic tissue. The serum RANKL level was significantly higher in healthy controls than in patients, and it was not related to osteoclastogenesis, thereby suggesting that RANKL is not involved in the bone metastatic mechanisms in gastric cancer. We hypothesized a role of RANKL in angiogenesis, thus we compared the serum levels of RANKL to those of VEGF, since VEGF is directly related to angiogenesis. Different from RANKL, the VEGF serum levels were higher in gastric patients than in controls, suggesting a block of the angiogenesis inhibition due to RANKL. RANKL and VEGF serum levels were not predictive of overall survival in our cohort of gastric patients.
胃癌是全球最常见和最致命的恶性肿瘤之一。与其他实体瘤相比，胃癌的骨转移并不常见，但发生时预后通常较差。不同成骨性癌症引起的骨转移中，破骨细胞生成和破骨细胞活性增加是常见特征。我们通过招募 31 名新诊断的胃癌患者和 45 名健康对照者，研究了胃癌中的破骨细胞生成及其机制。我们研究了患者和对照者外周血单个核细胞培养物中的体外破骨细胞生成，结果显示有一半的患者自发发生破骨细胞生成。这种破骨细胞生成与 RANKL 和 TNF-α无关。我们分析了胃癌的原发肿瘤和骨转移组织中参与破骨细胞生成的基因表达。与骨转移组织相比，转化生长因子-β（TGF-β）、骨保护素（OPG）、IL-7 和 Dickkopf-1（DKK-1）在原发肿瘤中的表达更高。RANKL 在原发肿瘤或骨转移组织中均不可检测。健康对照组的血清 RANKL 水平明显高于患者，且与破骨细胞生成无关，这表明 RANKL 不参与胃癌的骨转移机制。我们假设 RANKL 在血管生成中起作用，因此我们将 RANKL 血清水平与 VEGF 进行了比较，因为 VEGF 与血管生成直接相关。与 RANKL 不同，胃癌患者的血清 VEGF 水平高于对照组，这表明由于 RANKL 的作用，血管生成抑制被阻断。在我们的胃癌患者队列中，RANKL 和 VEGF 的血清水平与总生存期无关。
