Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis

Johanna A. Joyce, Amos Baruch, Kareem Chehade, Nicole Meyer-Morse, Enrico Giraudo, Fong Ying Tsai, Doron C. Greenbaum, Jeffrey H. Hager, Matthew Bogyo, Douglas Hanahan

Research output: Contribution to journalArticlepeer-review

Abstract

Tumors develop through successive stages characterized by changes in gene expression and protein function. Gene expression profiling of pancreatic islet tumors in a mouse model of cancer revealed upregulation of cathepsin cysteine proteases. Cathepsin activity was assessed using chemical probes allowing biochemical and in vivo imaging, revealing increased activity associated with the angiogenic vasculature and invasive fronts of carcinomas, and differential expression in immune, endothelial, and cancer cells. A broad-spectrum cysteine cathepsin inhibitor was used to pharmacologically knock out cathepsin function at different stages of tumorigenesis, impairing angiogenic switching in progenitor lesions, as well as tumor growth, vascularity, and invasiveness. Cysteine cathepsins are also upregulated during HPV16-induced cervical carcinogenesis, further encouraging consideration of this protease family as a therapeutic target in human cancers.

Original languageEnglish
Pages (from-to)443-453
Number of pages11
JournalCancer Cell
Volume5
Issue number5
DOIs
Publication statusPublished - May 2004

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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