Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia
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 o...
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Published in | The Prostate Vol. 57; no. 1; pp. 57 - 65 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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15.09.2003
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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.
METHODS
Primary prostatic stromal cells were grown in normal and hypoxic (1% O2) atmosphere. Activation of HIF 1 was evaluated after different time intervals by Western blot. Induced secretion of growth factors VEGF, FGF‐7, TGF‐β, IL 8, and FGF‐2 were analyzed by ELISA. To confirm the in vitro findings we also performed immunohistochemistry of HIF 1α as well as pro‐collagen I, collagens I, III, and IV in the benign tissue of radical prostatectomy specimens.
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‐β, FGF‐2, and IL 8 is increased under hypoxic in vitro conditions in comparison to normoxia. Levels of TGF‐β, 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 1α in (benign prostatic hyperplasia) BPH tissue revealed strong HIF 1α nuclear staining in hyperplastic areas. No difference was observed in the collagen pattern between hyperplastic and normal prostate tissue.
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. Prostate 57: 57–65, 2003. © 2003 Wiley‐Liss, Inc. |
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AbstractList | 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.
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‐β, IL 8, and FGF‐2 were analyzed by ELISA. To confirm the in vitro findings we also performed immunohistochemistry of HIF 1α as well as pro‐collagen I, collagens I, III, and IV in the benign tissue of radical prostatectomy specimens.
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‐β, FGF‐2, and IL 8 is increased under hypoxic in vitro conditions in comparison to normoxia. Levels of TGF‐β, 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 1α in (benign prostatic hyperplasia) BPH tissue revealed strong HIF 1α nuclear staining in hyperplastic areas. No difference was observed in the collagen pattern between hyperplastic and normal prostate tissue.
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. Prostate 57: 57–65, 2003. © 2003 Wiley‐Liss, Inc. 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. METHODS Primary prostatic stromal cells were grown in normal and hypoxic (1% O2) atmosphere. Activation of HIF 1 was evaluated after different time intervals by Western blot. Induced secretion of growth factors VEGF, FGF‐7, TGF‐β, IL 8, and FGF‐2 were analyzed by ELISA. To confirm the in vitro findings we also performed immunohistochemistry of HIF 1α as well as pro‐collagen I, collagens I, III, and IV in the benign tissue of radical prostatectomy specimens. 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‐β, FGF‐2, and IL 8 is increased under hypoxic in vitro conditions in comparison to normoxia. Levels of TGF‐β, 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 1α in (benign prostatic hyperplasia) BPH tissue revealed strong HIF 1α nuclear staining in hyperplastic areas. No difference was observed in the collagen pattern between hyperplastic and normal prostate tissue. 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. Prostate 57: 57–65, 2003. © 2003 Wiley‐Liss, Inc. 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. 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. 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. 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. BACKGROUNDLocal 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.METHODSPrimary 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.RESULTSHIF 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.CONCLUSIONSProstatic 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. |
Author | Rogatsch, Hermann Bektic, Jasmin Kofler, Kurt Steiner, Hannes Klocker, Helmut Berger, Andreas P. Bartsch, Georg |
Author_xml | – sequence: 1 givenname: Andreas P. surname: Berger fullname: Berger, Andreas P. email: andreas.p.berger@uibk.ac.at organization: Department of Urology, University of Innsbruck, Austria – sequence: 2 givenname: Kurt surname: Kofler fullname: Kofler, Kurt organization: Department of Urology, University of Innsbruck, Austria – sequence: 3 givenname: Jasmin surname: Bektic fullname: Bektic, Jasmin organization: Department of Urology, University of Innsbruck, Austria – sequence: 4 givenname: Hermann surname: Rogatsch fullname: Rogatsch, Hermann organization: Department of Pathology, University of Innsbruck, Austria – sequence: 5 givenname: Hannes surname: Steiner fullname: Steiner, Hannes organization: Department of Urology, University of Innsbruck, Austria – sequence: 6 givenname: Georg surname: Bartsch fullname: Bartsch, Georg organization: Department of Urology, University of Innsbruck, Austria – sequence: 7 givenname: Helmut surname: Klocker fullname: Klocker, Helmut organization: Department of Urology, University of Innsbruck, Austria |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12886524$$D View this record in MEDLINE/PubMed |
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Snippet | 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... 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... 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... BACKGROUNDLocal hypoxia may be one of the triggers of embryonic reawakening of the stroma and subsequent hyperplastic growth in the prostate. Using a cell... |
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SubjectTerms | benign prostatic hyperplasia Cell Line Collagen Type I - metabolism Collagen Type III - metabolism Collagen Type IV - metabolism DNA-Binding Proteins - metabolism DNA-Binding Proteins - secretion Endothelial Growth Factors - metabolism Endothelial Growth Factors - secretion FGF-2 FGF-7 Fibroblast Growth Factor 2 - metabolism Fibroblast Growth Factor 2 - secretion Fibroblast Growth Factor 7 Fibroblast Growth Factors - metabolism Fibroblast Growth Factors - secretion HIF 1 Human Growth Hormone - biosynthesis Humans hypoxia Hypoxia - metabolism Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit IL 8 Intercellular Signaling Peptides and Proteins - metabolism Intercellular Signaling Peptides and Proteins - secretion Interleukin-8 - metabolism Interleukin-8 - secretion Lymphokines - metabolism Lymphokines - secretion Male Nuclear Proteins - metabolism Nuclear Proteins - secretion Prostate - cytology Prostate - metabolism stromal cells Stromal Cells - cytology Stromal Cells - metabolism Stromal Cells - secretion TGF-β Transcription Factors Transforming Growth Factor beta - metabolism Transforming Growth Factor beta - secretion Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors VEGF |
Title | Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia |
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