Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer.

Background: Prostate tumors express high levels of transforming growth factor-beta1 (TGF-beta1) and seem to acquire resistance to its antiproliferative effects with tumor progression. Moreover, TGF-beta1 could be involved in tumor-promoting processes such as angiogenesis, cell migration, and immunosuppression.

Methods: Immunoreactivity for TGF-beta1 and its receptors type I and type II (TGFbeta-RI and TGFbeta-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-beta1 had shorter median cancer-specific survival than patients with normal TGF-beta1 immunoreactivity (5.0 vs. 10 years, P = 0.006). Furthermore, increased TGF-beta1 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 TGFbeta-RII expression in combination with TGF-beta1 overproduction showed particularly short survival (2.6 vs. 10 years, P = 0.0000), when compared to patients with normal immunoreactivity.

Conclusions: Overproduction of TGF-beta1 and loss of TGFbeta-RII expression are associated with poor clinical outcome in prostate cancer, and TGF-beta1 may promote tumor progression by stimulating angiogenesis and metastasis.