Androgen deprivation induces rapid involution and recovery of human prostate vasculature.
The response of the prostate tissue microenvironment to androgen deprivation (AD) represents a critical component in the treatment of benign prostatic hyperplasia and prostate cancer (CaP). Primary xenografts of human benign and CaP tissue transplanted to immunocompromized SCID mice were used to characterize the response of the prostate vasculature during the initial 14 days of AD. Microvessel density and vascular lumen diameter in the prostate xenografts decreased rapidly after AD, reached a nadir on days 2-4, and recovered between days 4 and 14. The number of apoptotic endothelial cells peaked on day 2 after AD and decreased to precastration levels over days 4-7. Leakage of vascular contents in the interstitial space was apparent between days 1 and 3 after AD; however, the vascular permeability barrier reestablished between days 7 and 14. Expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor-2, and basic fibroblast growth factor protein increased in endothelial cells between days 2 and 4 after AD, which preceded vascular recovery and appeared to be a direct and specific response of the endothelial cells to AD. Lack of comparable upregulation of these genes in primary cultures of human prostate endothelial cells in response to AD suggests a role for paracrine signaling mediated through stromal or epithelial cells. VEGF-A expression by prostate endothelial cells appears to represent a key facilitator of the vascular rebound in human prostate tissue induced by removal of circulating testicular androgens.
Godoy
Alejandro
A
Depatment of Urology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Montecinos
Viviana P
VP
Gray
Danny R
DR
Sotomayor
Paula
P
Yau
Jeffrey M
JM
Vethanayagam
R Robert
RR
Singh
Swaroop
S
Mohler
James L
JL
Smith
Gary J
GJ
D000728:Androgens / Q000172:deficiency*; D042501:Angiogenic Proteins / Q000096:biosynthesis; D000818:Animals; D002196:Capillaries / Q000473:pathology; D002478:Cells, Cultured; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011467:Prostate / Q000098:blood supply* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D012039:Regional Blood Flow / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000728:Androgens; D042501:Angiogenic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D013739:Testosterone; D005340:Fibrinogen