PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Abiatari, I.* ; DeOliveira, T.* ; Kerkadze, V.* ; Schwager, C.* ; Esposito, I. ; Giese, N.A.* ; Huber, P.* ; Bergman, F.* ; Abdollahi, A.* ; Friess, H.* ; Kleeff, J.*

Consensus transcriptome signature of perineural invasion in pancreatic carcinoma.

Mol. Cancer Ther. 8, 1494-1504 (2009)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
5.003
1.410
34
74
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter messenger-rna expression; cancer-cells; ductal adenocarcinoma; plexus invasion; breast-cancer; kif14; survival; cytokinesis; resection; growth
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 1535-7163
e-ISSN 1538-8514
Zeitschrift Molecular Cancer Therapeutics
Quellenangaben Band: 8, Heft: 6, Seiten: 1494-1504 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pathology (PATH)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-500300-001
DOI 10.1158/1535-7163.MCT-08-0755
Scopus ID 67649364195
PubMed ID 19509238
Erfassungsdatum 2009-12-31
[➜Korrektur melden]