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Basic Research

SOCS1 inhibits migration and invasion of prostate cancer cells, attenuates tumor growth and modulates the tumor stroma

Prostate Cancer and Prostatic Diseases volume 20, pages 36–47 (2017)Cite this article

Subjects

Abstract

Background:

The suppressor of cytokine signaling 1 (SOCS1) gene is repressed in prostate cancer (PCa) by epigenetic silencing and microRNA miR30d. Increased expression of the SOCS1-targeting miR30d correlates with higher biochemical recurrence, suggesting a tumor suppressor role of SOCS1 in PCa, but the underlying mechanisms are unclear. We have shown that SOCS1 inhibits MET receptor kinase signaling, a key oncogenic pathway in cancer progression. Here we evaluated the role of SOCS1 in attenuating MET signaling in PCa cells and tumor growth in vivo.

Methods:

MET-overexpressing human DU145 and PC3 PCa cell lines were stably transduced with SOCS1, and their growth, migration and invasion of collagen matrix were evaluated in vitro. Cells expressing SOCS1 or the control vector were evaluated for tumor growth in NOD.scid.gamma mice as xenograft or orthotopic tumors.

Results:

HGF-induced MET signaling was attenuated in SOCS1-expressing DU145 and PC3 cells. Compared with vector control cells, SOCS1-expressing cells showed reduced proliferation and impaired migration following HGF stimulation. DU145 and PC3 cells showed marked ability to invade the collagen matrix following HGF stimulation and this was attenuated by SOCS1. As xenografts, SOCS1-expressing PCa cells showed significantly reduced tumor growth compared with vector control cells. In the orthotopic tumor model, SOCS1 reduced the growth of primary tumors and metastatic spread. Intriguingly, the SOCS1-expressing DU145 and PC3 tumors showed increased collagen deposition, associated with increased frequency of myofibroblasts.

Conclusions:

Our findings support the tumor suppressor role of SOCS1 in PCa and suggest that attenuation of MET signaling is one of the underlying mechanisms. SOCS1 in PCa cells also appears to prevent the tumor-promoting functions of cancer-associated fibroblasts.

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Acknowledgements

We thank Dr Robert Day for providing PCa cell lines. AVH and RK are supported by Master’s degree scholarship from the Faculty of Medicine, Université de Sherbrooke. DB is a recipient of a postdoctoral fellowship from FRQS. CRCHUS is an FRQS-funded research center. This work was supported by Movember Discovery Grant from Prostate Cancer Canada (Grant number D2013-20).

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Author notes

  1. A Villalobos-Hernandez and D Bobbala: These authors contributed equally to this work.

Authors and Affiliations

  1. Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada

    A Villalobos-Hernandez, D Bobbala, R Kandhi, M G M Khan, M Mayhue, C M Dubois, S Ramanathan & S Ilangumaran

  2. Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada

    G Ferbeyre

  3. Department of Biochemistry, Faculty of Medicine, Université de Montreal, Montreal, Quebec, Canada

    C Saucier

  4. CRCHUS, Sherbrooke, Quebec, Canada

    S Ramanathan & S Ilangumaran

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  1. A Villalobos-Hernandez
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Villalobos-Hernandez, A., Bobbala, D., Kandhi, R. et al. SOCS1 inhibits migration and invasion of prostate cancer cells, attenuates tumor growth and modulates the tumor stroma. Prostate Cancer Prostatic Dis 20, 36–47 (2017). https://doi.org/10.1038/pcan.2016.50

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