首页> 外文期刊>Journal of orthopaedic research >Unique angiogenic and vasculogenic properties of renal cell carcinoma in a xenograft model of bone metastasis are associated with high levels of vegf-a and decreased ang-1 expression.
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Unique angiogenic and vasculogenic properties of renal cell carcinoma in a xenograft model of bone metastasis are associated with high levels of vegf-a and decreased ang-1 expression.

机译:在骨转移的异种移植模型中,肾细胞癌的独特血管生成和血管生成特性与高水平的vegf-a和降低的ang-1表达有关。

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摘要

Management of various tumor metastases to bone has dramatically improved, but this is not so for renal cell carcinoma (RCC), which is a difficult surgical problem due to its great vascularity. Furthermore, the unique mechanisms that mediate RCC vasculogenesis in bone remain unknown. To understand this process we developed a xenograft model that recapitulates highly vascular RCC versus less vascular tumors that metastasize to bone. Human tumor cell lines of RCC (786-O), prostate cancer (PC3), lung cancer (A549), breast cancer (MDA-MB231), and melanoma (A375) were transduced with firefly luciferase (Luc), injected into the tibiae of nude mice, and differences in growth, osteolysis, and vascularity were assessed by longitudinal bioluminescent imaging, micro-CT for measurement of calcified tissues and vascularity and histology. The results showed that while RCC-Luc has reduced growth and osteolytic potential versus the other tumor lines, it displayed a significant increase in vascular volume (p < 0.05). This expansion was due to 3- and 5-fold increases in small and large vessel numbers respectively. In vitro gene expression profiling revealed that RCC-Luc expresses significantly (p < 0.05) more vegf-a (10-fold) and 20- to 30-fold less ang-1 versus the other lines. These data demonstrate the utility of this model to study the unique vasculogenic properties of RCC bone metastases.
机译:各种肿瘤转移至骨骼的处理已得到显着改善,但对于肾细胞癌(RCC)则并非如此,由于其巨大的血管性,这是一个困难的手术问题。此外,介导骨中RCC血管生成的独特机制仍然未知。为了了解这一过程,我们开发了一种异种移植模型,该模型概括了高血管RCC与较少转移至骨的血管肿瘤。用萤火虫荧光素酶(Luc)转导RCC(786-O),前列腺癌(PC3),肺癌(A549),乳腺癌(MDA-MB231)和黑素瘤(A375)的人肿瘤细胞系,并将其注入胫骨通过纵向生物发光成像,微型CT测量钙化组织,血管和组织学,评估裸鼠的生长,骨溶解和血管的差异。结果表明,尽管RCC-Luc与其他肿瘤系相比,生长和溶骨潜能有所降低,但其血管体积却显着增加(p <0.05)。这种膨胀是由于小血管和大血管数量分别增加了3倍和5倍。体外基因表达谱分析显示,RCC-Luc与其他品系相比,Ang-1的Ang-1表达量高得多(p <0.05),而ang-1则少表达20-30倍。这些数据表明该模型可用于研究RCC骨转移的独特血管生成特性。

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