The molecular basis of pancreatic fibrosis: common stromal gene expression in chronic pancreatitis and pancreatic adenocarcinoma.
OBJECTIVE
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 epithelial-stromal signaling in pancreatic desmoplasia and may serve as diagnostic or therapeutic targets.
Binkley
Charles E
CE
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Zhang
Lizhi
L
Greenson
Joel K
JK
Giordano
Thomas J
TJ
Kuick
Rork
R
Misek
Dave
D
Hanash
Samir
S
Logsdon
Craig D
CD
Simeone
Diane M
DM
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000465:Algorithms; D045744:Cell Line, Tumor; D002908:Chronic Disease; D016000:Cluster Analysis; D003550:Cystic Fibrosis / Q000235:genetics*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005796:Genes / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D042282:Microdissection / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D010179:Pancreas / Q000473:pathology / Q000502:physiology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010195:Pancreatitis / Q000235:genetics*