TITLE

Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility

AUTHOR(S)
Thompson, C. C.; Ashcroft, F. J.; Patel, S.; Saraga, G.; Vimalachandran, D.; Prime, W.; Campbell, F.; Dodson, A.; Jenkins, R. E.; Lemoine, N. R.; Crnogorac-Jurcevic, T.; Yin, H. L.; Costello, E.
PUB. DATE
January 2007
SOURCE
Gut;Jan2007, Vol. 56 Issue 1, p95
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells. Aims: To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines. Methods: CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays. Results: Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n=44 patients) and malignant (n=69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p<0.001) and cytoplasmic (p<0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n=24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p<0.001). High nuclear CapG was associated with increased tumour size (p =0.001). High nuclear gelsolin was associated with reduced survival (p =0.0]). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility. Conclusions: Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.
ACCESSION #
23627627

 

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