title: Differential expression of VEGF ligands and receptors in prostate cancer.
abstract: BACKGROUND
  Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer.
  
  
  METHODS
  The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer.
  
  
  RESULTS
  Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue.
  
  
  CONCLUSIONS
  These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer.
authors.affiliation: Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Woollard
authors.forename: Kenneth
authors.initials: K
authors.lastname: Opeskin
authors.forename: Sanja
authors.initials: S
authors.lastname: Coso
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Megan E
authors.initials: ME
authors.lastname: Baldwin
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Williams
mesh_terms: D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000502:physiology; D008207:Lymphatic Metastasis / Q000473:pathology; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000556:secondary; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3