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.
Department of Urology and Andrology, Umeå University, Sweden.
P
P
Wikström
P
P
Stattin
I
I
Franck-Lissbrant
J E
JE
Damber
A
A
Bergh
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology
D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta