Zhang Shuangli, Li Baolin, Tang Wei, Ni Linying, Ma Huili, Lu Ming, Meng Qinggang
Department of Orthopaedic Surgery, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Department of Orthopaedic Surgery, Harbin The First Hospital, Harbin Medical University, Harbin, Heilongjiang 150010, P.R. China.
Oncol Lett. 2018 Aug;16(2):2305-2311. doi: 10.3892/ol.2018.8960. Epub 2018 Jun 13.
Previous studies have demonstrated that connective tissue growth factor (CTGF) is expressed at increased levels in prostate cancer bone metastasis mouse models and patients with prostate cancer which metastasizes to the bone; however, the underlying molecular mechanism(s) remain unknown. The present study investigated the function of CTGF in osteoblast differentiation and its effect on prostate cancer bone metastasis by analyzing gene expression and transcription at different levels of invasion, metastasis of prostate cancer cells, and the influence of CTGF on proliferation and xenotransplantation. A mouse model demonstrating bone metastasis was used to investigate the function(s) of CTGF in bone metastasis and osteoblast differentiation. Results demonstrated that expression was increased in association with high bone metastasis in prostate cancer cells, and its expression was significantly decreased in whole cell lysates. expression in prostate cancer cells with high levels of bone metastasis was increased 1.9-fold compared with prostate cancer cells with low levels of bone metastasis. The expression of CTGF in mesenchymal cells was markedly increased compared with epithelial cells. Results indicated that the increased expression of CTGF does not affect the proliferation of tumor cells and possesses no influence on tumor volume. Control and CTGF plasmids were transfected into RM1 cells and led to 4 and 17% bone lesions, respectively. Increased expression of CTGF significantly enlarged the tumor area in the bone metastatic position compared with the control. Positive areas of alkaline phosphatase were significantly decreased as the concentration of CTGF increased. The results of the present study demonstrated that CTGF promotes prostate carcinoma to metastasize in the bone by dysregulating osteoblast differentiation.
先前的研究表明，在前列腺癌骨转移小鼠模型以及发生骨转移的前列腺癌患者中，结缔组织生长因子（CTGF）的表达水平升高；然而，其潜在的分子机制仍不清楚。本研究通过分析前列腺癌细胞侵袭、转移不同水平的基因表达和转录情况，以及CTGF对增殖和异种移植的影响，研究了CTGF在成骨细胞分化中的功能及其对前列腺癌骨转移的作用。使用一个显示骨转移的小鼠模型来研究CTGF在骨转移和成骨细胞分化中的功能。结果表明，CTGF的表达与前列腺癌细胞的高骨转移相关，且在全细胞裂解物中其表达显著降低。与低骨转移水平的前列腺癌细胞相比，高骨转移水平的前列腺癌细胞中CTGF的表达增加了1.9倍。与上皮细胞相比，间充质细胞中CTGF的表达明显增加。结果表明，CTGF表达的增加不影响肿瘤细胞的增殖，对肿瘤体积也没有影响。将对照质粒和CTGF质粒转染到RM1细胞中，分别导致4%和17%的骨损伤。与对照组相比，CTGF表达的增加显著扩大了骨转移部位的肿瘤面积。随着CTGF浓度的增加，碱性磷酸酶的阳性面积显著减少。本研究结果表明，CTGF通过失调成骨细胞分化促进前列腺癌在骨中转移。
