The molecular basis of pancreatic fibrosis: Common stromal gene expression in chronic pancreatitis and pancreatic adenocarcinoma

Charles E. Binkley, Lizhi Zhang, Joel K. Greenson, Thomas J. Giordano, Rork Kuick, Dave Misek, Samir Hanash, Craig D. Logsdon, Diane M. Simeone

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Objectives: Tissue desmoplasia occurs in a number of disease states, but its molecular basis is poorly understood. To determine which genes are overexpressed in cells contained within the desmoplastic stroma of pancreatic adenocarcinoma and chronic pancreatitis, we undertook genetic profiling of microdissected tissue samples of pancreatic adenocarcinoma, chronic pancreatitis, normal pancreas, and pancreatic cancer cell lines. We observed that samples of both pancreatic adenocarcinoma and chronic pancreatitis showed elevated expression of many shared genes compared with the normal pancreas. We hypothesized that these common genes likely important in stromal production and/or function could be identified using a strategy that involved comparisons between pancreatic adenocarcinoma, chronic pancreatitis, normal pancreas, and pancreatic cancer cell lines. Methods: We performed oligonucleotide microarray analysis of 6800 different genes expressed in 10 samples of pancreatic adenocarcinoma, 5 samples of normal pancreas, 5 samples of chronic pancreatitis, and 7 pancreatic cancer cell lines. Microarray findings were validated with RT-PCR, and immunohistochemistry was used to verify protein localization to the stromal compartment of both pancreatic cancer and chronic pancreatitis. Results: We employed a deductive comparison whereby genes expressed in the normal pancreas and pancreatic cancer cell lines were selectively eliminated from those expressed in common by pancreatic adenocarcinoma and chronic pancreatitis. This strategy identified 107 genes predicted to be expressed within cells of the stromal compartment of both pancreatic adenocarcinoma and chronic pancreatitis. Conclusions: These genes are likely important factors in epithelialstromal signaling in pancreatic desmoplasia and may serve as diagnostic or therapeutic targets.

Original languageEnglish (US)
Pages (from-to)254-263
Number of pages10
JournalPancreas
Volume29
Issue number4
DOIs
StatePublished - Nov 1 2004

Keywords

  • Gene expression
  • Pancreatic adenocarcinoma
  • Stroma

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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    Binkley, C. E., Zhang, L., Greenson, J. K., Giordano, T. J., Kuick, R., Misek, D., Hanash, S., Logsdon, C. D., & Simeone, D. M. (2004). The molecular basis of pancreatic fibrosis: Common stromal gene expression in chronic pancreatitis and pancreatic adenocarcinoma. Pancreas, 29(4), 254-263. https://doi.org/10.1097/00006676-200411000-00003