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(American Journal of Pathology. 2004;165:1129-1139.)
© 2004 American Society for Investigative Pathology

Tissue Plasminogen Activator in Murine Exocrine Pancreas Cancer

Selective Expression in Ductal Tumors and Contribution to Cancer Progression

Susana Aguilar*, Josep M. Corominas{dagger}, Núria Malats{ddagger}, José A. Pereira§, Marlène Dufresne, Francisco X. Real*§ and Pilar Navarro*

From Unitat de Biologia Cellular i Molecular,* Institut Municipal d’Investigació Mèdica, Barcelona; the Departament de Patologia,{dagger} Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona; Unitat de Recerca Respiratòria i Ambiental,{ddagger} Institut Municipal d’Investigació Mèdica, Barcelona; the Departament de Ciències Experimentals i de la Salut,§ Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain; and INSERM U531, Institut Louis Bugnard, Toulouse, France

Tissue plasminogen activator (tPA) is absent from normal human pancreas and is expressed in 95% of human pancreatic adenocarcinomas. We have analyzed the expression of components of the tPA system in murine pancreatic tumors and the role of tPA in neoplastic progression. Transgenic mice expressing T antigen and c-myc under the control of the elastase promoter (Ela1-TAg and Ela1-myc, respectively) were used. tPA was undetectable in normal pancreas, acinar dysplasia, ductal complexes, and in all acinar tumors. By contrast, it was consistently detected in Ela1-myc tumors showing ductal differentiation. Crossing transgenic Ela1-myc with tPA–/– mice had no effect on the proportion of ductal tumors, indicating that tPA is not involved in the acinar-to-ductal transition. Ela1-myc:tPA–/– mice showed an increased survival in comparison to control mice. All ductal tumors, and none of the acinar tumors, overexpressed the tPA receptor annexin A2, suggesting its participation in the effects mediated by tPA. Our findings indicate that murine and human pancreatic ductal tumors share molecular alterations in the tPA system that may play a role in tumor progression.




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E. Ortiz-Zapater, S. Peiro, O. Roda, J. M. Corominas, S. Aguilar, C. Ampurdanes, F. X. Real, and P. Navarro
Tissue Plasminogen Activator Induces Pancreatic Cancer Cell Proliferation by a Non-Catalytic Mechanism That Requires Extracellular Signal-Regulated Kinase 1/2 Activation through Epidermal Growth Factor Receptor and Annexin A2
Am. J. Pathol., May 1, 2007; 170(5): 1573 - 1584.
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