Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
DOI
PMC
 |
|
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
messenger-rna expression; cancer-cells; ductal adenocarcinoma; plexus invasion; breast-cancer; kif14; survival; cytokinesis; resection; growth
ISSN (print) / ISBN
1535-7163
e-ISSN
1538-8514
Zeitschrift
Molecular Cancer Therapeutics
Quellenangaben
Band: 8,
Heft: 6,
Seiten: 1494-1504
Verlag
American Association for Cancer Research (AACR)
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pathology (PATH)