Expression of vascular endothelial growth factor by human renal cancer cells enhances angiogenesis of primary tumors and production of ascites but not metastasis to the lungs in nude mice
H. Kanayama et al., Expression of vascular endothelial growth factor by human renal cancer cells enhances angiogenesis of primary tumors and production of ascites but not metastasis to the lungs in nude mice, CLIN EXP M, 17(10), 1999, pp. 831-840
We determined the role that vascular endothelial growth factor (VEGF), also
known as vascular permeability factor (VPF), plays in the progression of h
uman renal cell cancer in nude mice. Low metastatic and low VEGF/VPF-expres
sing human renal cancer cells SN12C were transfected with the VEGF165 cDNA
or plasmid alone as control. VEGF165-transfected SN12C cells produced large
amounts of biologically active VEGF in culture that did not affect cell do
ubling time or confluence. Subsequent to implantation into the renal subcap
sule of nude mice, the VEGF165-transfected SN12C cells produced fast-growin
g (PCNA labeling), large tumors that expressed high levels of VEGF/VPF and
were well vascularized (CD3-positive vessels). The tumors produced hyperper
meability of peritoneal blood vessels (Evans blue dye-leak assay), bloody a
scites, and short survival time. Parental or control transfected SN12C cell
s produced less vascularized, slower growing tumors with no ascites. Regard
less of in vivo expression level of VEGF, the incidence of spontaneous lung
metastasis was low, suggesting that in itself, the expression of VEGF/VPF
by renal cancer cells is not sufficient to produce metastasis.