Consensus transcriptome signature of perineural invasion in pancreatic carcinoma
| Autor: | Irene Esposito, Tiago DeOliveira, Christian Schwager, Amir Abdollahi, Ivane Abiatari, Vachtang Kerkadze, Jörg Kleeff, Nathalia A. Giese, Peter E. Huber, Frank Bergman, Helmut Friess |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Small interfering RNA Immunoblotting Perineural invasion Kinesins Biology Transcriptome Pancreatic tumor Cell Movement Pancreatic cancer Cell Line Tumor medicine Animals Cluster Analysis Humans rho-Specific Guanine Nucleotide Dissociation Inhibitors Neoplasm Invasiveness Cell Proliferation Guanine Nucleotide Dissociation Inhibitors Oligonucleotide Array Sequence Analysis Oncogene Proteins Gene knockdown Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Tumor Suppressor Proteins Vagus Nerve Anatomy medicine.disease Anoikis Immunohistochemistry Rats Gene Expression Regulation Neoplastic Pancreatic Neoplasms Oncology Cancer research CA19-9 RNA Interference |
| Zdroj: | Molecular cancer therapeutics. 8(6) |
| ISSN: | 1538-8514 |
| Popis: | 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 β (ARHGDIβ) in perineural invasion was confirmed on RNA and protein levels in human pancreatic tumor specimens. We found significant up-regulation of KIF14 and ARHGDIβ 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 ARHGDIβ 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 ARHGDIβ. [Mol Cancer Ther 2009;8(6):1494–1504] |
| Databáze: | OpenAIRE |
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