| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2023086 | Regulatory Peptides | 2009 | 5 Pages |
BackgroundRecently it was demonstrated that transforming growth factor β2 (TGF-β2) is the predominant TGF-β isoform in the human prostate. However, with the human prostatic cancer cells PC-3 mostly effects of TGF-β1 were investigated. This study aimed to analyze the effects of TGF-β2 on its own secretion, on the secretion of plasminogen activator inhibitor-1 (PAI-1), and the matrix metalloproteinases (MMP)-2 and MMP-9 in comparison to stimulations with TGF-β1.Materials and methodsPC-3 cells were cultured with and without TGF-β1 and TGF-β2 to analyze autostimulation and their effects on protein secretion. ELISAs for TGF-β1, TGF-β2, TGF-β3, PAI-1, MMP-2 and MMP-9 were used to analyze protein levels in the supernatant. Cell proliferation was determined with a proliferation assay.ResultsA dose-dependent and significant suppression of cell proliferation with TGF-β1 (p < 0.05) and TGF-β2 (p < 0.05) was observed. PC-3 cells secrete higher amounts of total TGF-β2 compared to total TGF-β1. Only for TGF-β2, we found the active isoform. In contrast, the secretion of TGF-β3 was not detectable. Additionally, we observed a strong and significant increase in the secretion of MMP-9 and PAI-1 after stimulations with TGF-β1 and TGF-β2, respectively. However, no protein levels of MMP-2 were detectable.ConclusionOur experiments revealed that TGF-β2 is the predominant TGF-β isoform in PC-3 cells. Furthermore, a strong effect of TGF-β1 and TGF-β2 on the secretion of MMP-9 and PAI-1 was found. Thus, PC-3 cells not only secrete TGF-β1 and TGF-β2 but also respond to stimulations with the TGF-β isoforms. The interesting observation that only TGF-β2 is activated points to different mechanisms of proteolytic activation of the diverse TGF-β isoforms.
