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Polymorphonuclear neutrophils promote dyshesion of tumor cells and elastase-mediated degradation of E-cadherin in pancreatic tumors.
Gaida, Matthias M; Steffen, Thomas Große; Günther, Frank; Tschaharganeh, Darjus F; Felix, Klaus; Bergmann, Frank; Schirmacher, Peter; Hänsch, Gertrud M.
Afiliação
  • Gaida MM; Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Eur J Immunol ; 42(12): 3369-80, 2012 Dec.
Article em En | MEDLINE | ID: mdl-23001948
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) presenting with a micropapillary growth pattern is frequently associated with a prominent neutrophil infiltration into the tumor. The relevance of neutrophil infiltrates for tumor progression, however, is still debated. To gain insight into the role of polymorphonuclear neutrophils (PMNs) in PDAC, we assessed their effect on pancreatic tumor cells grown in vitro as monolayers. Time-lapse video microscopy showed a PMN-induced dyshesion of the tumor cells, and subsequent experiments revealed that this dyshesion was due to PMN elastase-mediated degradation of E-cadherin, an adhesion molecule that mediates the intercellular contact of the tumor cells. E-cadherin degradation by elastase or--(for comparison) down-modulation by specific siRNA, significantly increased the migratory capacity of the pancreatic tumor cells, leading to the hypothesis that PMNs could contribute to the invasive tumor growth. To address this issue, biopsies of patients with PDAC (n = 112) were analyzed. We found that E-cadherin expression correlated negatively with PMN infiltration, compatible with the notion that E-cadherin is cleaved by PMN-derived elastase, which in turn could result in the dispersal of the tumor cells, enhanced migratory capacity and thus invasive tumor growth.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Caderinas / Elastase de Leucócito / Carcinoma Ductal Pancreático / Proteólise / Proteínas de Neoplasias / Neutrófilos Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Caderinas / Elastase de Leucócito / Carcinoma Ductal Pancreático / Proteólise / Proteínas de Neoplasias / Neutrófilos Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2012 Tipo de documento: Article