Inhibition of transforming growth factor-beta activity decreases angiogenesis in a human prostate cancer-reactive stroma xenograft model.
We have shown previously that reactive stroma promotes angiogenesis and growth of LNCaP human prostate tumors in the differential reactive stroma xenograft model. Regulators of reactive stroma are not known, but transforming growth factor (TGF)-beta1 is a likely candidate. Three-way differential reactive stroma tumors were generated in the presence of TGF-beta1 latency-associated peptide (LAP) or TGF-beta1 neutralizing antibody. Tumors treated with either of those TGF-beta inhibitors exhibited a reduction in blood vessels, and blood lakes were observed in some areas. The microvessel density of LAP-treated tumors was decreased 3.5-fold relative to control tumors. Moreover, the average wet-weight of LAP-treated tumors was reduced 46% compared with control tumors. The results of this study suggest that TGF-beta regulates reactive stroma and its ability to promote angiogenesis and tumor growth.
Tuxhorn
Jennifer A
JA
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
McAlhany
Stephanie J
SJ
Yang
Feng
F
Dang
Truong D
TD
Rowley
David R
DR
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D011498:Protein Precursors / Q000494:pharmacology; D017154:Stromal Cells / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D010446:Peptide Fragments; D011498:Protein Precursors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1