TY - JOUR
T1 - 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
AU - Xie, Chao
AU - Schwarz, Edward M.
AU - Sampson, Erik R.
AU - Dhillon, Robinder S.
AU - Li, Dan
AU - O'Keefe, Regis J.
AU - Tyler, Wakenda
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - bone metastasis
KW - renal cell carcinoma (RCC)
KW - vasculogenesis
KW - xenograft
UR - http://www.scopus.com/inward/record.url?scp=83855162887&partnerID=8YFLogxK
U2 - 10.1002/jor.21500
DO - 10.1002/jor.21500
M3 - Article
C2 - 21809376
AN - SCOPUS:83855162887
SN - 0736-0266
VL - 30
SP - 325
EP - 333
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 2
ER -