Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors

Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors

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Abstract Background Prostate cancer metastasizes to regional lymph nodes and distant here sites but the roles of lymphatic and hematogenous pathways in metastasis are not fully understood.Methods We studied the roles of VEGF-C and VEGFR3 in prostate cancer metastasis by blocking VEGFR3 using intravenous adenovirus-delivered VEGFR3-Ig fusion protein (VEGFR3-Ig) and by ectopic expression of VEGF-C in PC-3 prostate tumors in nude mice.Results VEGFR3-Ig decreased the density of lymphatic capillaries in orthotopic PC-3 tumors (p p p p Conclusion The data suggest that even though VEGF-C/VEGFR3 pathway is primarily required for lymphangiogenesis and lymphatic metastasis, an increased level of VEGF-C can also stimulate angiogenesis, which is associated with growth of orthotopic prostate tumors and a switch from a primary pattern here of lymph node metastasis to an increased proportion of metastases at distant sites.