Open Access

Evaluation of clinical colon carcinoma using activity-based proteomic profiling

  • Melissa C. Zhang1,
  • Jiangyue Wu1,
  • Kristin G. Ardlie2 and
  • Emme C. K. Lin1Email author
Clinical Proteomics1:13104301

DOI: 10.1385/CP:1:3-4:301

Abstract

The evaluation of clinical tumor tissues is a valuable approach to discovering novel drug targets because of the direct relevance of human samples. We used activity-based proteomic profiling (ABPP) to study the differences in serine hydrolase activities from 12 matched pairs of clinical normal and tumor colon tissues. Unlike traditional proteomics or measures of mRNA abundance, ABPP actually quantifies enzymatic activities, a characteristic crucial for drug targeting. Several serine hydrolases were differentially active in tumor vs normal tissues, despite a lack of obvious corresponding alterations in protein expression. We identified one tumor-specific activity by mass spectrometry to be fibroblast activation protein (FAP), an integral membrane serine protease that has been reported to be present only in tumor stroma or during wound healing and absent in normal tissues. FAP activity was further found to be approximately twofold higher in stage III relative to stage II colon cancer, suggestive of a role in tumor progression. We were also able to identify other proteins, some of which had not been previously linked to cancer, which had higher activity in tumors. Our results demonstrate the applicability of ABPP for the efficient identification of multiple clinical disease targets.

Key Words

Tumor activity proteomics colorectal adenocarcinoma serine hydrolase

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