Surveying proteolytic processes in human cancer microenvironments by microdialysis and activity-based mass spectrometry

Markus Hardt, David K. Lam, John C. Dolan, Brian L. Schmidt

Research output: Contribution to journalArticle

Abstract

Purpose: We present a strategy to survey proteolytic processes that occur in human cancer microenvironments. Experimental design: In situ microdialysis during oral cancer surgery was combined with mass spectrometry-based proteomics to analyze interstitial fluid surrounding tumors and anatomically matched normal sites. Protease activity-based 18O-profiling was utilized to reveal peptides that were processed by co-collected proteases ex vivo. Results: We demonstrated for the first time the use of microdialysis in humans to collect interstitial fluid from cancer microenvironments. Proteomic profiling identified proteases and inhibitors in the microdialysis samples. A subset of peptides displayed characteristic 18O-isotope patterns that indicated processing by endogenous proteases. Conclusions and clinical relevance: The presented approach provides unprecedented views of in vivo targets of proteases without disrupting the cancer or surrounding tissue. The methodology can be broadly adapted to other physiological conditions in which proteolytic mediators are involved (e.g. arthritic joints, inflamed muscle, other types of cancer) and where a comparison of normal and pathological tissue is sought.

Original languageEnglish (US)
Pages (from-to)636-643
Number of pages8
JournalProteomics - Clinical Applications
Volume5
Issue number11-12
DOIs
StatePublished - Dec 2011

Keywords

  • Cancer
  • Microdialysis
  • Pain

ASJC Scopus subject areas

  • Clinical Biochemistry

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