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

被引:87
作者
Dhar, Gopal
Mehta, Smita
Banerjee, Snlgdha
Gardner, Ashleigh
McCarty, Bryan M.
Mathur, Sharad C.
Campbell, Donald R.
Kambhampati, Suman
Banerjee, Sushanta K.
机构
[1] Vet Adm Med Ctr, Canc Res Unit, Kansas City, MO 64128 USA
[2] Dept Hematol & Oncol, Kansas City, KS USA
[3] Dept Pathol, Kansas City, KS USA
[4] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA
[5] Univ Missouri, St Lukes Hosp, Kansas City, KS USA
关键词
pancreatic adenocarcinoma; WISP-2/CCN5; p53 tumor suppressor gene;
D O I
10.1016/j.canlet.2007.02.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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. Published by Elsevier Ltd.
引用
收藏
页码:63 / 70
页数:8
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