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Open Access Green as soon as Postprint is submitted to ZB.
Consensus transcriptome signature of perineural invasion in pancreatic carcinoma.
Mol. Cancer Ther. 8, 1494-1504 (2009)
Perineural invasion, the growth of tumor cells along nerves, is a key feature of pancreatic cancer. The cardinal symptom of pancreatic cancer, abdominal pain often radiating to the back, as well as the high frequency of local tumor recurrence following resection are both attributed to the unique ability of pancreatic tumor cells to invade the neuronal system. The molecular mechanisms underlying the neuroaffinity of pancreatic tumors are not completely understood. In this study, we developed a novel method to monitor ex vivo perineural invasion into surgically resected rat vagal nerves by different human pancreatic tumor cell lines. Genome-wide transcriptional analyses were employed to identify the consensus set of genes differentially regulated in all highly nerve-invasive (nerve invasion passage 3) versus less invasive (nerve invasion passage 0) pancreatic tumor cells. The critical involvement of kinesin family member 14 (KIF14) and Rho-GDP dissociation inhibitor beta (ARHGDI beta) in perineural invasion was confirmed on RNA and protein levels in human pancreatic tumor specimens. We found significant up-regulation of KIF14 and ARHGDI beta mRNA levels in patients with pancreatic cancer, and both proteins were differentially expressed in tumor cells invading the perineural niche of pancreatic cancer patients as detected by immunohistochemistry. Moreover, functional knockdown of KIF14 and ARHGDI beta using small interfering RNA resulted in altered basal and/or perineural invasion of pancreatic tumor cells. Our work provides novel insights into the molecular determinants of perineural invasion in pancreatic cancer. The established nerve invasion model and the consensus signature of perineural invasion could be instrumental in the identification of novel therapeutic targets of pancreatic cancer as exemplified by KIF14 and ARHGDI beta.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
messenger-rna expression; cancer-cells; ductal adenocarcinoma; plexus invasion; breast-cancer; kif14; survival; cytokinesis; resection; growth
Language
english
Publication Year
2009
HGF-reported in Year
2009
ISSN (print) / ISBN
1535-7163
e-ISSN
1538-8514
Journal
Molecular Cancer Therapeutics
Quellenangaben
Volume: 8,
Issue: 6,
Pages: 1494-1504
Publisher
American Association for Cancer Research (AACR)
Reviewing status
Peer reviewed
Institute(s)
Institute of Pathology (PATH)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-500300-001
Scopus ID
67649364195
PubMed ID
19509238
Erfassungsdatum
2009-12-31