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The CLIP-CHIP™: A Focused Oligonucleotide Microarray Platform for Transcriptome Analysis of the Complete Human and Murine Cancer Degradomes

  • Reinhild Kappelhoff
  • Claire H. Wilson
  • Christopher M. Overall

Abstract

By modifying the secretome, cancer disturbs normal tissue homeostasis leading to pathological changes, often driven by perturbed proteolysis. Besides the traditional dogma of tumor promotion and metastasis through degradation of the extracellular matrix, extracellular proteases are now recognized to play more important roles as signaling molecules that modulate the web of cytokines and growth factors that orchestrate extracellular homeostasis and cell proliferation, adhesion, migration, differentiation, apoptosis, and evasion from the immune system. Although proteases have long been regarded as promising drug targets in cancer, increasingly it is being recognized that many proteases have beneficial roles in mitigating the detrimental effects of cancer, classifying these proteases as drug anti-targets. Discrimination of protease drug targets and anti-targets in cancer is therefore critical for understanding oncogenesis and for drug development programs. Complicating target and anti-target identification, is the fact that proteases do not act in isolation, but interact in pathways, circuits and cascades with other proteases to form the protease web. The CLIP-CHIP™ is the only microarray platform that focuses on all proteases, non-proteolytic homologues, and protease inhibitors in the human and mouse genomes making it an ideal platform for an unbiased transcriptomic analysis of the cancer degradome — the complete repertoire of proteases and inhibitors expressed in cancer, reactive stromal cells, and normal tissue — and the changes wrought in the protease web by cancer. By analysis of cancer-type-specific expression profiles of proteases and inhibitors, the CLIP-CHIP oligonucleotide-based microarray assists in understanding how proteases modulate the tumor and the enveloping secretome.

Keywords

Microarray Platform Microarray Chip cDNA Microarray Data Complete Repertoire Proteolytic Potential 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Reinhild Kappelhoff
    • 1
  • Claire H. Wilson
    • 2
  • Christopher M. Overall
    • 3
  1. 1.Centre for Blood Research, Department of Oral Biological and Medical SciencesUniversity of British ColumbiaVancouverCanada
  2. 2.Centre for Blood Research, Department of Biochemistry and Molecular BiologyUniversity of British ColumbiaVancouverCanada
  3. 3.Centre for Blood Research, Departments of Oral Biological and Medical Sciences; Biochemistry and Molecular BiologyUniversity of British ColumbiaVancouverCanada

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