Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice.

Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice.
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前列腺特异性膜抗原可促进小鼠前列腺癌细胞体内骨转移

DOI:
10.1590/s0100-879x2012007500085
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发表时间:
2012-08
期刊:
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
影响因子:
--
通讯作者:
Qiu SP
Qiu SP
中科院分区:
其他
文献类型:
--
作者:
Zhao LY;Mao XP;Chao KY;Guo SJ;Qiu SP

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关于前列腺特异性膜抗原(PSMA)是否以及如何影响前列腺癌(PCa)体内骨转移的报道尚不充分。在本研究中,作者在小鼠前列腺癌细胞系RM-1中诱导了PSMA的稳定表达。6周龄雌性C57BL/6小鼠37只,体重(22.45±0.456) g,在体内诱发骨转移,将RM-1细胞主动注射到股骨腔内,导致双侧股骨骨密度不对称。病理检查骨组织中也检测到肿瘤细胞。对骨密度的影响表现为注射rM-PSMA细胞组(0.0738±0.0185 g/cm~2)和注射空质粒细胞组(0.0895±0.0241 g/cm~2)之间的显著差异。RM-PSMA组溶骨性病变发生率(68.4%)高于对照组(27.8%)。免疫组织化学结果显示,rM-PSMA组血管内皮生长因子(VEGF)和基质金属蛋白酶-9(MMP-9)的表达明显高于对照组,而体外培养的rM-PSMA组的血管内皮生长因子(VEGF)和基质金属蛋白酶-9(MMP-9)的表达高于对照组。因此,本研究首次提出并证实PSMA可通过增加对PCa细胞的硬化性破坏来促进PCa的体内骨转移。进一步的分析还表明,PSMA通过增加体内骨转移瘤中基质金属蛋白酶-9和血管内皮生长因子的表达,对RM-1的侵袭能力起积极作用。
Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm2) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm2). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo.
DOI: 10.1038/84643
发表时间: 2001-02-01
期刊: NATURE MEDICINE
影响因子: 82.9
作者:
Skobe, M;Hawighorst, T;Detmar, M
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