You are here

Article Text

Article menu
Download PDFPDF
Pancreas
PRSS3 promotes tumour growth and metastasis of human pancreatic cancer
  1. Guozhong Jiang1,2,
  2. Fengyu Cao1,
  3. Guoping Ren3,
  4. Dongling Gao1,
  5. Vipul Bhakta2,
  6. Yunhan Zhang1,
  7. Hua Cao4,
  8. Ziming Dong1,
  9. Weidong Zang1,
  10. Shuijun Zhang4,
  11. Han Hsi Wong2,
  12. Crispin Hiley2,
  13. Tatjana Crnogorac-Jurcevic2,
  14. Nick R Lemoine1,2,
  15. Yaohe Wang1,2
  1. 1Sino-British Research Centre for Molecular Oncology, Department of Pathology, Zhengzhou University, China
  2. 2Centre for Molecular Oncology & Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  3. 3Department of Surgical Pathology, The First Teaching Hospital of Zhejiang University, Hangzhou, China
  4. 4Department of Otolaryngology, The First Affiliated Hospital of Zhengzhou University, China
  1. Correspondence to Dr Yaohe Wang and Professor Nick Lemoine, Centre for Molecular Oncology & Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, Barbican, London EC1M 6BQ, UK; yaohe.wang{at}qmul.ac.uk

Abstract

Background and aims Metastasis accounts for the poor outcome of patients with pancreatic cancer. We recently discovered PRSS3 to be over-expressed in metastatic human pancreatic cancer cells. This study aimed to elucidate the role of PRSS3 in the growth and metastasis of human pancreatic cancer.

Methods PRSS3 expression in human pancreatic cancer cell lines was detected by qPCR and immunoblotting. The effect of PRSS3 on cancer cell proliferation, migration and invasion in vitro, tumour growth and metastasis in vivo were investigated by manipulation of PRSS3 expression in human pancreatic cancer cell lines. VEGF expression was detected by ELISA, and the pathway through which PRSS3 regulates VEGF expression was investigated. The therapeutic effect of targeting this pathway on metastasis was assessed in vivo. Immunohistochemistry was employed to detect PRSS3 expression in human pancreatic cancer tissues.

Results PRSS3 was over-expressed in the metastatic PaTu8988s cell line, but not in the non-metastatic PaTu8988t cell line. Over-expression of PRSS3 promoted pancreatic cancer cell proliferation as well as invasion in vitro, and tumour progression and metastasis in vivo. Stepwise investigations demonstrated that PRSS3 upregulates VEGF expression via the PAR1-mediated ERK pathway. ERK inhibitor significantly delayed the progression of metastases of pancreatic cancer and prolonged the survival of animals bearing metastatic pancreatic cancer (p<0.05). 40.54% of human pancreatic cancers (n=74) were positive for PRSS3 protein. A significant correlation was observed between PRSS3 expression and metastasis (p<0.01). Multivariate Cox regression analysis indicated that patients with PRSS3 expression in their tumours had a shorter survival time compared to those without PRSS3 expression (p<0.05).

Conclusion PRSS3 plays an important role in the progression, metastasis and prognosis of human pancreatic cancer. Targeting the PRSS3 signalling pathway may be an effective and feasible approach for treatment of this lethal cancer.

  • Pancreatic cancer
  • PRSS3
  • VEGF
  • ERK
  • metastasis
  • gene expression
  • gene targeting
  • pancreatic tumours

https://doi.org/10.1136/gut.2009.200105

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Funding This project is supported by the Nature Sciences Foundation of China (30530800), Cancer Research UK (C633-A6253/A6251) and Barts & The London Charity.

    • Competing interests None.

    • Ethics approval This study was conducted with the approval of the host institutions.

    • Provenance and peer review Not commissioned; externally peer reviewed.