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TGF Beta1 Expression Correlates with Survival and Tumor Aggressiveness of Prostate Cancer

  • Urologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although biopsy Gleason score and clinical stage can be used to inform treatment decisions for prostate cancer, identifying molecular markers of tumor aggressiveness could lead to a more tailored approaches to therapy. In the present study, we investigated the association of transforming growth factor (TGF)-β1 levels and various markers of tumor aggressiveness and explore some potential mechanisms underlying the associations.

Methods

We used human and murine prostate cancer cell lines and their respective hormone resistance sub-lines, in vitro and in vivo to examine the changes in tumor aggressiveness, as well as the pathway responsible for these changes. Furthermore, 105 prostate cancer biopsy specimens were analyzed to correlate the level of TGF-β1 with the clinical characteristics of patients.

Results

Our data revealed that activated TGF-β1 signaling resulted in more aggressive tumor growth and augmented the epithelial–mesenchymal transition. Activated IL-6 signaling was associated with TGF-β1 levels and the aggressive tumor features noted in TGF-β1-positive prostate cancers in vitro and in vivo. Furthermore, the TGF-β1 levels significantly correlated with Tregs accumulation in vivo. The clinical data indicated that TGF-β1 immunoreactivity had a moderate positive correlation with IL-6 staining, advanced clinical stage, higher Gleason score, and pretreatment PSA in patients with prostate cancer.

Conclusions

TGF-β1 levels are significantly associated with aggressive prostate features. In vitro and in vivo alternations of TGF-β1 expression impacts tumor invasiveness, tumor growth rate and recruitment of immunosuppressive Treg cells in the tumor microenvironment. TGF-β1 expression may represent a clinical useful biomarker to guide prostate cancer treatment decisions.

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Acknowledgments

The study was supported by National Science Council, Taiwan. Grant 101-2314-B-182-062-MY3.

Disclosure

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. Department of Urology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan

    Chun-Te Wu MD, PhD

  2. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Chun-Te Wu MD, PhD, Ying-Hsu Chang MD, Wei-Yu Lin MD, Wen-Cheng Chen MD & Miao-Fen Chen MD, PhD

  3. Department of Urology, Chang Gung Memorial Hospital at Linko, Linko, Taiwan

    Ying-Hsu Chang MD

  4. Department of Urology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan

    Wei-Yu Lin MD

  5. Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan

    Wen-Cheng Chen MD & Miao-Fen Chen MD, PhD

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  1. Chun-Te Wu MD, PhD
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  2. Ying-Hsu Chang MD
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Correspondence to Miao-Fen Chen MD, PhD.

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Wu, CT., Chang, YH., Lin, WY. et al. TGF Beta1 Expression Correlates with Survival and Tumor Aggressiveness of Prostate Cancer. Ann Surg Oncol 22 (Suppl 3), 1587–1593 (2015). https://doi.org/10.1245/s10434-015-4804-9

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  • DOI: https://doi.org/10.1245/s10434-015-4804-9

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