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Gut 61:1315-1322 doi:10.1136/gutjnl-2011-300544
  • Pancreas
  • Original article

Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models

  1. Craig D Logsdon1,4
  1. 1Department of Cancer Biology, MD Anderson Cancer Center, Houston, Texas, USA
  2. 2Department of Radiology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA
  3. 3Pathology, MD Anderson Cancer Center, Houston, Texas, USA
  4. 4GI Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Professor Craig D Logsdon, Department of Cancer Biology, MD Anderson Cancer Center, 1515 Holcombe Boulevard., Unit 953, Houston, TX 77030-4009, USA; clogsdon{at}mdanderson.org
  1. Contributors ZCM and WRAE contributed to the study concept and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of the manuscript for important intellectual content and final approval of the version to be published. TG, DD, BJ and TA contributed to the study concept and design, critical revision of the manuscript for important intellectual content and final approval of the version to be published. HW contributed to the acquisition of data, pathology support, analysis and interpretation of data, critical revision of the manuscript for important intellectual content and final approval of the version to be published. CHT and CDL contributed to the study concept and design, analysis and interpretation of data, drafting of manuscript, critical revision of manuscript for important intellectual content, obtained funding, study supervision and final approval of the version to be published.

  • Revised 20 September 2011
  • Accepted 5 October 2011
  • Published Online First 7 November 2011

Abstract

Background and Aims Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. Surgical resection is the only effective treatment; however, only 20% of patients are candidates for surgery. The ability to detect early PDAC would increase the availability of surgery and improve patient survival. This study assessed the feasibility of using the enzymatic activity of cathepsin E (Cath E), a protease highly and specifically expressed in PDAC, as a novel biomarker for the detection of pancreas-bearing pancreatic intraepithelial neoplasia (PanIN) lesions and PDAC.

Methods Pancreas from normal, chronic pancreatitis and PDAC patients was assessed for Cath E expression by quantitative real-time PCR and immunohistochemistry. Human PDAC xenografts and genetically engineered mouse models (GEMM) of PDAC were injected with a Cath E activity selective fluorescent probe and imaged using an optical imaging system.

Results The specificity of Cath E expression in PDAC patients and GEMM of pancreatic cancer was confirmed by quantitative real-time PCR and immunohistochemistry. The novel probe for Cath E activity specifically detected PDAC in both human xenografts and GEMM in vivo. The Cath E sensitive probe was also able to detect pancreas with PanIN lesions in GEMM before tumour formation.

Conclusions The elevated Cath E expression in PanIN and pancreatic tumours allowed in-vivo detection of human PDAC xenografts and imaging of pancreas with PanIN and PDAC tumours in GEMM. Our results support the usefulness of Cath E activity as a potential molecular target for PDAC and early detection imaging.

Footnotes

  • ZC-M and WRA-E contributed equally to this work.

  • Funding This research was supported by funds from the Lockton Endowment (to CDL), the MDACC CCSG CA#16672 (to CDL) and by NIH CA135312 (to CHT).

  • Competing interests None.

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

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