Consensus transcriptome signature of perineural invasion in pancreatic carcinoma.

Abiatari, Ivane and DeOliveira, Tiago and Kerkadze, Vachtang and Schwager, Christian and Esposito, Irene and Giese, Nathalia A and Huber, Peter and Bergman, Frank and Abdollahi, Amir and Friess, Helmut and Kleeff, Jörg (2009) Consensus transcriptome signature of perineural invasion in pancreatic carcinoma. Molecular cancer therapeutics, 8 (6). pp. 1494-504. ISSN 1538-8514

[img] Text
2009_Mol_Cancer_Ther_Abiatari et al.pdf

Download (766kB)


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 (ARHGDIbeta) in perineural invasion was confirmed on RNA and protein levels in human pancreatic tumor specimens. We found significant up-regulation of KIF14 and ARHGDIbeta 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 ARHGDIbeta 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 ARHGDIbeta.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Depositing User: Dr Ivane Abiatari
Date Deposited: 30 Apr 2015 05:27
Last Modified: 30 Apr 2015 05:27

Actions (login required)

View Item View Item