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

¹ Division of Surgery and Oncology, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK
² Cancer Tissue Bank Research Centre, Department of Pathology, University of Liverpool, Liverpool, UK
³ Department of Pathology, University of Liverpool, Liverpool, UK
⁴ Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
⁵ Cancer Research UK Molecular Oncology Unit, Barts and the London School of Medicine and Dentistry, London, UK
⁶ University of Texas Southwestern Medical Centre, Dallas, Texas, USA

Correspondence to:
Correspondence to:
E Costello
Division of Surgery and Oncology, Royal Liverpool University Hospital, 5th Floor UCD Building, Daulby Street, University of Liverpool, Liverpool L68 3 GA, UK;ecostell{at}liv.ac.uk

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.

Abbreviations: IQR, interquartile range; MALDI-TOF, matrix-assisted laser desorption/ionisation-time-of–flight; MTT, 3-(4, 5-dimethythiazol-2-yl-2, 5-diphenyltetrazolium bromide)