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Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia.
- Source :
-
The Prostate [Prostate] 2003 Sep 15; Vol. 57 (1), pp. 57-65. - Publication Year :
- 2003
-
Abstract
- Background: Local hypoxia may be one of the triggers of embryonic reawakening of the stroma and subsequent hyperplastic growth in the prostate. Using a cell culture model of human prostatic stromal cells, we investigated the effects of hypoxia on activation of hypoxia-inducible factor 1 (HIF 1) and on the production of growth factors.<br />Methods: Primary prostatic stromal cells were grown in normal and hypoxic (1% O(2)) atmosphere. Activation of HIF 1 was evaluated after different time intervals by Western blot. Induced secretion of growth factors VEGF, FGF-7, TGF-beta, IL 8, and FGF-2 were analyzed by ELISA. To confirm the in vitro findings we also performed immunohistochemistry of HIF 1alpha as well as pro-collagen I, collagens I, III, and IV in the benign tissue of radical prostatectomy specimens.<br />Results: HIF 1 is activated in a time-dependent manner, already starting 1 hr after exposure of stromal cells to hypoxic conditions. Secretion of VEGF, FGF-7, TGF-beta, FGF-2, and IL 8 is increased under hypoxic in vitro conditions in comparison to normoxia. Levels of TGF-beta, VEGF, and IL 8 were rapidly and statistically significantly increased in the supernatant of hypoxic cells. Consistent with the in vitro findings, immunohistochemistry of HIF 1alpha in (benign prostatic hyperplasia) BPH tissue revealed strong HIF 1alpha nuclear staining in hyperplastic areas. No difference was observed in the collagen pattern between hyperplastic and normal prostate tissue.<br />Conclusions: Prostatic stromal cells respond to hypoxia by upregulation of secretion of several growth factors suggesting that hypoxia can trigger prostatic growth. Therefore, hypoxia might be a key factor contributing to the pathogenesis of BPH.<br /> (Copyright 2003 Wiley-Liss, Inc.)
- Subjects :
- Cell Line
Collagen Type I metabolism
Collagen Type III metabolism
Collagen Type IV metabolism
DNA-Binding Proteins metabolism
Endothelial Growth Factors metabolism
Fibroblast Growth Factor 2 metabolism
Fibroblast Growth Factor 7
Fibroblast Growth Factors metabolism
Humans
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Intercellular Signaling Peptides and Proteins metabolism
Interleukin-8 metabolism
Lymphokines metabolism
Male
Nuclear Proteins metabolism
Prostate cytology
Stromal Cells cytology
Transforming Growth Factor beta metabolism
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Human Growth Hormone biosynthesis
Hypoxia metabolism
Prostate metabolism
Stromal Cells metabolism
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 0270-4137
- Volume :
- 57
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 12886524
- Full Text :
- https://doi.org/10.1002/pros.10279