Research Papers:
SerpinB3 upregulates the Cyclooxygenase-2 / β-Catenin positive loop in colorectal cancer
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Abstract
Liliana Terrin1, Marco Agostini2,3,4, Mariagrazia Ruvoletto1, Andrea Martini1, Salvatore Pucciarelli2, Chiara Bedin3, Donato Nitti2, Patrizia Pontisso1
1Department of Medicine, University of Padua, Italy
2Surgery Branch, Department of Surgery Oncology and Gastroenterology, University of Padua, Italy
3Nano-Inspired Biomedicine Lab, Istituto di Ricerca Pediatrica - Città della Speranza, Padua, Italy
4Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA
Correspondence to:
Patrizia Pontisso, email: [email protected]
Liliana Terrin, email: [email protected]
Keywords: colorectal cancer, SerpinB3, COX-2, β-Catenin, tumor stage
Received: June 29, 2016 Accepted: January 03, 2017 Published: February 02, 2017
ABSTRACT
Colorectal cancer is characterized by aberrant Cyclooxigenase-2 (COX-2) and β-Catenin pathways. Recently, the protease inhibitor SerpinB3 has been described overexpressed in more advanced stages of this tumor. Aim of the study was to explore the possible relationship between these molecules in this setting. We evaluated colorectal cancer specimens from 105 patients and a positive correlation between SerpinB3, COX-2 and β-Catenin expression was observed, with higher levels in tumor than in adjacent tissue. The highest levels were associated with pathologic parameters of poor prognosis, including vascular invasion, lymph node metastasis and perineural invasion. The molecular and protein profiles of COX-2 and β-Catenin were analyzed in cell lines with different expression of SerpinB3. In those with high expression of SerpinB3, COX-2 and β-Catenin were higher than in controls. Cells with high levels of SerpinB3 showed higher proliferation and invasion compared to controls. In conclusion, in colorectal cancer SerpinB3, COX-2 and β-Catenin are positively correlated and associated with more advanced tumor stage. The in vitro experimental results support a driving role of SerpinB3 in the upregulation of COX-2/ β-Catenin positive loop, associated with a more aggressive cellular phenotype.
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PII: 14997