Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma.
Ilona Kohler,Peter Bronsert,Sylvia Timme,Martin Werner,Martin Werner,Thomas Brabletz,Thomas Brabletz,Ulrich T. Hopt,Oliver Schilling,Dirk Bausch,Tobias Keck,Ulrich F. Wellner +11 more
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TLDR
Experimental data suggest an important role of epithelial‐mesenchymal transition (EMT) in invasion and metastasis of PDAC and biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head are suggested.Abstract:
Background and Aim
Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head.
Methods
Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis.
Results
Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor–host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis.
Conclusions
Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor–host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.read more
Citations
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Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.
Hanane Laklai,Yekaterina A. Miroshnikova,Michael W. Pickup,Eric A. Collisson,Grace E. Kim,Alexander S. Barrett,Ryan C. Hill,Johnathon N. Lakins,David D. Schlaepfer,Janna K. Mouw,Valerie S. LeBleu,Nilotpal Roy,Sergey V. Novitskiy,Julia S. Johansen,Valeria Poli,Raghu Kalluri,Christine A. Iacobuzio-Donahue,Laura D. Wood,Matthias Hebrok,Kirk C. Hansen,Harold L. Moses,Valerie M. Weaver +21 more
TL;DR: The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.
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Tumor Budding: The Name is EMT. Partial EMT.
TL;DR: Based on recent literature, indicating a co-expression of epithelial and mesenchymal markers in many tumor buds, it is posited that tumor budding is a manifestation of this hybrid epithelial/mesenchyal phenotype displaying collective cell migration.
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Chemoresistance in Pancreatic Cancer.
TL;DR: New perspectives for enhancing the efficacy of gemcitabine are outlined after reviewing the related factors of gem citabine metabolism, mechanism of action, and chemoresistance.
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Tumor budding in colorectal cancer—ready for diagnostic practice?
TL;DR: A practical, evidence-based proposal for the assessment of tumor budding in the daily sign-out is outlined and the current knowledge of the molecular characteristics of high-grade budding tumors in the context of personalized treatment approaches and biomarker discovery is summarized.
Neuroendocrine neoplasms of the pancreas: clinical, pathologic and cross-sectional imaging analysis according to the 4 th edition of the World Health Organization (WHO) classification of tumors of the digestive system
TL;DR: Poster: "ECR 2012 / C-2310 / Neuroendocrine neoplasms of the pancreas: clinical, pathologic and cross-sectional imaging analysis according to the 4th edition of the World Health Organization classification of tumors of the digestive system"
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Raghu Kalluri,Robert A. Weinberg +1 more
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Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
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The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs
Ulrich F. Wellner,Jörg Schubert,Ulrike Burk,Otto Schmalhofer,Feng Zhu,Annika G Sonntag,Bettina Waldvogel,Corinne Vannier,Douglas S. Darling,Axel zur Hausen,Valerie G. Brunton,Jennifer P. Morton,Owen J. Sansom,Julia Schüler,Marc P. Stemmler,Christoph Herzberger,Ulrich T. Hopt,Tobias Keck,Simone Brabletz,Thomas Brabletz +19 more
TL;DR: It is proposed that ZEB1 links EMT-activation and stemness-maintenance by suppressingstemness-inhibiting microRNAs (miRNAs) and thereby is a promoter of mobile, migrating cancer stem cells.
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