Loss of WISP-2/CCN5 signaling in human pancreatic cancer: A potential mechanism for epithelial-mesenchymal-transition

• Published in: Cancer letters 2007-08, Vol.254 (1), p.63-70
• Main Authors: Dhar, Gopal, Mehta, Smita, Banerjee, Snigdha, Gardner, Ashleigh, McCarty, Bryan M, Mathur, Sharad C, Campbell, Donald R, Kambhampati, Suman, Banerjee, Sushanta K
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Blotting, Northern; Blotting, Western; CCN Intercellular Signaling Proteins; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell Line, Tumor; Disease Progression; Epithelium - metabolism; Epithelium - pathology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; In Situ Hybridization; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Medical research; Mesoderm - metabolism; Mesoderm - pathology; p53 tumor suppressor gene; Pancreas; Pancreas - chemistry; Pancreas - metabolism; Pancreas - pathology; Pancreatic adenocarcinoma; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatitis, Chronic - genetics; Pancreatitis, Chronic - metabolism; Pancreatitis, Chronic - pathology; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Repressor Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - genetics; Signal Transduction - physiology; Studies; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; WISP-2/CCN5
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2007.02.012

Abstract The objective of this study was to explore the pathophysiological relevance of WISP-2/CCN5 in progression of human pancreatic adenocarcinoma (PAC). We found WISP-2/CCN5 mRNA and protein expression was faint and sporadic in PAC and detected in only 8.7–20% of the samples with varying grades as compared to adjacent normal and chronic pancreatitis samples where expression was very high in the ducts and acini. Colocalization studies in tissue-microarray slides revealed WISP-2/CCN5 mRNA loss was associated with p53 overexpression in PAC. Like tissue samples, p53 mutant-PAC cell lines show loss of WISP-2/CCN5. Moreover, functional analysis studies demonstrate exposure of pancreatic cancer cells to WISP-2/CCN5 recombinant protein enhances mesenchymal–epithelial-transition (MET). Collectively, we suggest WISP-2/CCN5 silencing may be a critical event during differentiation and progression of PAC and mutant p53 is possibly an important player in pursuing this episode.