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

作者：Xie Chao; Schwarz Edward M; Sampson Erik R; Dhillon Robinder S; Li Dan; O'Keefe Regis J; Tyler Wakenda^*

来源：Journal of Orthopaedic Research, 2012, 30(2): 325-333.

DOI：10.1002/jor.21500

• renal cell carcinoma (RCC)
• vasculogenesis
• bone metastasis
• xenograft

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.

• 出版日期2012-2