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Inhibition of Transforming Growth Factor-ß Activity Decreases Angiogenesis in a Human Prostate Cancer-reactive Stroma Xenograft Model¹

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

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)-ß1 is a likely candidate. Three-way differential reactive stroma tumors were generated in the presence of TGF-ß1 latency-associated peptide (LAP) or TGF-ß1 neutralizing antibody. Tumors treated with either of those TGF-ß 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-ß regulates reactive stroma and its ability to promote angiogenesis and tumor growth.

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