Vasoactive intestinal peptide enhances growth and angiogenesis of human experimental prostate cancer in a xenograft model.
We show that vasoactive intestinal peptide (VIP) exerts trophic and proangiogenic activities in experimental prostate cancer in vivo. Nude mice were subcutaneously injected with Matrigel impregnated with LNCaP prostate cancer cells. Cell treatment with 100 nM VIP for 1h before xenograft resulted in increased tumor growth after 8 and, more remarkably, 15 days of injection. The same occurred with the mRNA expression of the main angiogenic factor, vascular endothelial growth factor (VEGF), as shown by real-time RT-PCR quantification. The proangiogenic activity of VIP was further established by showing increases of hemoglobin levels, Masson trichromic staining, and immunohistochemical CD34 staining in tumors excised 15 days after subcutaneous injection of VIP-treated cells as compared to control conditions. All these parameters indicate that VIP increases vessel formation. This xenograft model is a useful tool to study in vivo the effects of VIP-related peptides in tumor growth and development of blood supply as well as their therapeutical potential in prostate cancer.
Collado
Beatriz
B
Department of Biochemistry and Molecular Biology, University of Alcalá, Alcalá de Henares 28871, Spain.
Carmena
María J
MJ
Clemente
Celia
C
Prieto
Juan C
JC
Bajo
Ana M
AM
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D018952:Antigens, CD34; D006454:Hemoglobins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014660:Vasoactive Intestinal Peptide