DOI: 10.1097/01.mpa.0000193779.96475.f4
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Issn Print: 0885-3177
Publication Date: 2005/11/01
THE ACTIN CAPPING PROTEINS, CAPG AND GELSOLIN, ARE OVEREXPRESSED IN PANCREATIC CANCER: IMPLICATIONS FOR CANCER CELL MOTILITY AND PATIENT SURVIVAL
C Thompson; F Ashcroft; G Saraga; D Vimalachandran; S Patel; W Prime; F Campbell; A Dodson; R E Jenkins; N R Lemoine; T Crnogorac-Jurcevic; H L Yin; J P Neoptolemos; E Costello
+ Author Information
Author Information: Division of Surgery and Oncology,
Excerpt
Pancreatic ductal adenocarcinoma is characterised by extensive local invasion and metastasis. Using proteomic analysis we discovered that CapG, an actin regulatory protein with a known role in cell motility, is overexpressed in pancreatic cancer. CapG was identified by mass spectrometry following excision from two-dimensional gels, where it appeared as several isoforms. The identification was confirmed by two-dimensional Western analysis. Immunohistochemical analysis of benign (n = 44 patients) and malignant pancreatic ductal cells (n = 69 patients) demonstrated significantly higher CapG staining intensity in both nuclear (P < 0.0001) and cytoplasmic (P < 0.0001) compartments of malignant cells. RNAi-mediated reduction of CapG expression in pancreatic cancer cell lines was accompanied by significantly impaired cell migration and/or impaired wound healing. However, there was no significant association between high CapG levels in primary tumours and invasion or patient survival, prompting us to determine whether gelsolin, another motility modulating protein in the same family as CapG, with significant structural and functional homology to CapG, might also be overexpressed in pancreatic cancer. High gelsolin expression was detected by immunostaining in 85% of malignant (58/68 patients) compared to only 12.5% of benign (3/24 patients) ducts. There was considerable overlap in the expression of gelsolin and CapG in the cytoplasmic compartment of tumour cells. While gelsolin expression was not significantly associated with invasion, its overexpression in the nucleus was associated with reduced survival (P = 0.028). Our data indicate significant upregulation of actin capping proteins in pancreatic cancer cells. This may have important consequences for their motility and consequently their dissemination, and in the case of gelsolin would appear to be deleterious.
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