Nuclear factor-κB-mediated transforming growth factor-β-induced expression of vimentin is an independent predictor of biochemical recurrence after radical prostatectomy

Qiang Zhang*, Brian T. Helfand, Thomas L. Jang, Lihua J. Zhu, Lin Chen, Ximing J. Yang, James Kozlowski, Norm Smith, Shilajit D. Kundu, Guangyu Yang, Adekunle A. Raji, Borko Javonovic, Michael Pins, Paul Lindholm, Yinglu Guo, William J. Catalona, Chung Lee

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Purpose: Transforming growth factor-β (TGF-β)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-β and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-β-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before. Experimental Design: We analyzed TGF-β-induced EMT using nuclear factor-κB (NF-κB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-β signaling components and EMT-related factors were analyzed using specific antibodies. Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy. Results: In prostate cancer cell lines, TGF-β-induced EMT was mediated by NF-κB signaling. Blockade of NF-κB or TGF-β signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-β1, vimentin, and NF-κB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients' Gleason score. Conclusions: The detection of NF-κB-mediated TGF-β-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-β signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.

Original languageEnglish (US)
Pages (from-to)3557-3567
Number of pages11
JournalClinical Cancer Research
Volume15
Issue number10
DOIs
StatePublished - May 15 2009

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Transforming Growth Factors
Vimentin
Prostatectomy
Epithelial-Mesenchymal Transition
Recurrence
Prostatic Neoplasms
Neoplasms
Tissue Array Analysis
Keratin-18
Cell Line
Antibodies
Neoplasm Grading
Research Design
Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{1594d21a972a4f67905a270d68fbb262,
title = "Nuclear factor-κB-mediated transforming growth factor-β-induced expression of vimentin is an independent predictor of biochemical recurrence after radical prostatectomy",
abstract = "Purpose: Transforming growth factor-β (TGF-β)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-β and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-β-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before. Experimental Design: We analyzed TGF-β-induced EMT using nuclear factor-κB (NF-κB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-β signaling components and EMT-related factors were analyzed using specific antibodies. Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy. Results: In prostate cancer cell lines, TGF-β-induced EMT was mediated by NF-κB signaling. Blockade of NF-κB or TGF-β signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-β1, vimentin, and NF-κB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients' Gleason score. Conclusions: The detection of NF-κB-mediated TGF-β-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-β signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.",
author = "Qiang Zhang and Helfand, {Brian T.} and Jang, {Thomas L.} and Zhu, {Lihua J.} and Lin Chen and Yang, {Ximing J.} and James Kozlowski and Norm Smith and Kundu, {Shilajit D.} and Guangyu Yang and Raji, {Adekunle A.} and Borko Javonovic and Michael Pins and Paul Lindholm and Yinglu Guo and Catalona, {William J.} and Chung Lee",
year = "2009",
month = "5",
day = "15",
doi = "10.1158/1078-0432.CCR-08-1656",
language = "English (US)",
volume = "15",
pages = "3557--3567",
journal = "Clinical Cancer Research",
issn = "1078-0432",
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}

Nuclear factor-κB-mediated transforming growth factor-β-induced expression of vimentin is an independent predictor of biochemical recurrence after radical prostatectomy. / Zhang, Qiang; Helfand, Brian T.; Jang, Thomas L.; Zhu, Lihua J.; Chen, Lin; Yang, Ximing J.; Kozlowski, James; Smith, Norm; Kundu, Shilajit D.; Yang, Guangyu; Raji, Adekunle A.; Javonovic, Borko; Pins, Michael; Lindholm, Paul; Guo, Yinglu; Catalona, William J.; Lee, Chung.

In: Clinical Cancer Research, Vol. 15, No. 10, 15.05.2009, p. 3557-3567.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nuclear factor-κB-mediated transforming growth factor-β-induced expression of vimentin is an independent predictor of biochemical recurrence after radical prostatectomy

AU - Zhang, Qiang

AU - Helfand, Brian T.

AU - Jang, Thomas L.

AU - Zhu, Lihua J.

AU - Chen, Lin

AU - Yang, Ximing J.

AU - Kozlowski, James

AU - Smith, Norm

AU - Kundu, Shilajit D.

AU - Yang, Guangyu

AU - Raji, Adekunle A.

AU - Javonovic, Borko

AU - Pins, Michael

AU - Lindholm, Paul

AU - Guo, Yinglu

AU - Catalona, William J.

AU - Lee, Chung

PY - 2009/5/15

Y1 - 2009/5/15

N2 - Purpose: Transforming growth factor-β (TGF-β)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-β and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-β-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before. Experimental Design: We analyzed TGF-β-induced EMT using nuclear factor-κB (NF-κB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-β signaling components and EMT-related factors were analyzed using specific antibodies. Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy. Results: In prostate cancer cell lines, TGF-β-induced EMT was mediated by NF-κB signaling. Blockade of NF-κB or TGF-β signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-β1, vimentin, and NF-κB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients' Gleason score. Conclusions: The detection of NF-κB-mediated TGF-β-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-β signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.

AB - Purpose: Transforming growth factor-β (TGF-β)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-β and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-β-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before. Experimental Design: We analyzed TGF-β-induced EMT using nuclear factor-κB (NF-κB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-β signaling components and EMT-related factors were analyzed using specific antibodies. Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy. Results: In prostate cancer cell lines, TGF-β-induced EMT was mediated by NF-κB signaling. Blockade of NF-κB or TGF-β signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-β1, vimentin, and NF-κB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients' Gleason score. Conclusions: The detection of NF-κB-mediated TGF-β-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-β signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.

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