Article Text
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 = 0.01). 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.
- IQR, interquartile range
- MALDI-TOF, matrix-assisted laser desorption/ionisation-time-of–flight
- MTT, 3-(4, 5-dimethythiazol-2-yl-2, 5-diphenyltetrazolium bromide)
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Footnotes
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↵* These authors contributed equally to this work.
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Published Online First 17 July 2006
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Funding: This work is supported by grants from Cancer Research UK, North West Cancer Research Fund, The Medical Research Council and the National Institute of Health Burn Centre grant P05GM21681.
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Competing interests: None.
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Ethical approval: The study was conducted with ethical approval from Cheshire and Merseyside Health Authority (Hamilton House, 24 Pall Mall, Liverpool L3 6AL, UK), LREC ref 03/02/316A.