The actin binding protein destrin is associated with growth and perineural invasion of pancreatic cancer.
OBJECTIVE
The small actin-binding protein destrin is one of the key regulators involved in remodeling of the actin cytoskeleton, a process crucial for cytokinesis, cell migration and polarized cell growth as well as for cancer cell migration and invasion.


METHODS
A novel ex vivo nerve invasion model mirroring perineural cancer cell invasion as a key feature of pancreatic ductal adenocarcinoma has been previously established. Using this model, highly nerve-invasive clones of human pancreatic cancer cell lines have been obtained. Genome-wide transcriptional analyses of these cells revealed up-regulation of destrin in highly versus lowly nerve-invasive pancreatic cancer cells.


RESULTS
Increased expression of destrin in these nerve-invasive cells was validated using quantitative RT-PCR and immunoblotting; concomitant changes in cell morphology were demonstrated using immunofluorescence analysis. Silencing of destrin by two specific siRNA oligonucleotides in Panc-1 pancreatic cancer cells decreased invasiveness and migration, and reduced proliferation of these cells.


CONCLUSIONS
Destrin is upregulated in nerve-invasive pancreatic cancer cells and its expression might be related to perineural invasiveness.
Department of Surgery, Technische Universität München, Munich, Germany.
Theresa
T
Klose
Ivane
I
Abiatari
Tamar
T
Samkharadze
Tiago
T
De Oliveira
Carsten
C
Jäger
Merab
M
Kiladze
Nataliya
N
Valkovskaya
Helmut
H
Friess
Christoph W
CW
Michalski
Jörg
J
Kleeff
D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051345:Destrin / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009420:Nervous System / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
D051345:Destrin; D034741:RNA, Small Interfering