title: 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.
abstract: 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.
authors.affiliation: Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Xie
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.forename: Erik R
authors.initials: ER
authors.lastname: Sampson
authors.forename: Robinder S
authors.initials: RS
authors.lastname: Dhillon
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Wakenda
authors.initials: W
authors.lastname: Tyler
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply* / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse