Quiescin sulfhydryl oxidase 1 promotes invasion of pancreatic tumor cells mediated by matrix metalloproteinases

Benjamin A. Katchman, Kwasi Antwi, Galen Hostetter, Michael J. Demeure, Aprill Watanabe, G. Anton Decker, Laurence J. Miller, Daniel D. Von Hoff, Douglas F. Lake

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Quiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. We previously mapped a peptide in plasma from pancreatic ductal adenocarcinoma (PDA) patients back to an overexpressed QSOX1parent protein. In addition to overexpression in pancreatic cancer cell lines, 29 of 37 patients diagnosed with PDA expressed QSOX1 protein in tumor cells, but QSOX1 was not detected in normal adjacent tissues or in a transformed, but nontumorigenic cell line. To begin to evaluate the advantage QSOX1 might provide to tumors, we suppressed QSOX1 protein expression using short hairpin (sh) RNA in two pancreatic cancer cell lines. Growth, cell cycle, apoptosis, invasion, and matrix metalloproteinase (MMP) activity were evaluated. QSOX1 shRNA suppressed both short and long isoforms of the protein, showing a significant effect on cell growth, cell cycle, and apoptosis. However, QSOX1 shRNA dramatically inhibited the abilities of BxPC-3 and Panc-1 pancreatic tumor cells to invade through Matrigel in a modified Boyden chamber assay. Mechanistically, gelatin zymography indicated that QSOX1 plays an important role in activation of MMP-2 and MMP-9. Taken together, our results suggest that the mechanism of QSOX1-mediated tumor cell invasion is by activation of MMP-2 and MMP-9.

Original languageEnglish (US)
Pages (from-to)1621-1631
Number of pages11
JournalMolecular Cancer Research
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Katchman, B. A., Antwi, K., Hostetter, G., Demeure, M. J., Watanabe, A., Decker, G. A., Miller, L. J., Von Hoff, D. D., & Lake, D. F. (2011). Quiescin sulfhydryl oxidase 1 promotes invasion of pancreatic tumor cells mediated by matrix metalloproteinases. Molecular Cancer Research, 9(12), 1621-1631. https://doi.org/10.1158/1541-7786.MCR-11-0018