Transforming growth factor β1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer

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Abstract
BACKGROUND Prostate tumors express high levels of transforming growth factor‐β1 (TGF‐β1) and seem to acquire resistance to its antiproliferative effects with tumor progression. Moreover, TGF‐β1 could be involved in tumor‐promoting processes such as angiogenesis, cell migration, and immunosuppression. METHODS Immunoreactivity for TGF‐β1 and its receptors type I and type II (TGFβ‐RI and TGFβ‐RII), tumor vascular count, and cell proliferation were studied in 73 cases of prostate cancer, diagnosed between 1975–1983 and followed with surveillance. RESULTS Patients with tumor overproduction of TGF‐β1 had shorter median cancer‐specific survival than patients with normal TGF‐β1 immunoreactivity (5.0 vs. 10 years, P = 0.006). Furthermore, increased TGF‐β1 staining was associated with tumor grade, high vascular counts, and metastasis (P = 0.02, 0.02, and 0.01, respectively). Patients with loss of tumor TGFβ‐RII expression in combination with TGF‐β1 overproduction showed particularly short survival (2.6 vs. 10 years, P = 0.0000), when compared to patients with normal immunoreactivity. CONCLUSIONS Overproduction of TGF‐β1 and loss of TGFβ‐RII expression are associated with poor clinical outcome in prostate cancer, and TGF‐β1 may promote tumor progression by stimulating angiogenesis and metastasis. Prostate 37:19–29, 1998.