T-cadherin loss promotes experimental metastasis of squamous cell carcinoma

Philippova, M. and Pfaff, D. and Kyriakakis, E. and Buechner, S. A. and Iezzi, G. and Spagnoli, G. C. and Schoenenberger, A. W. and Erne, P. and Resink, T. J.. (2013) T-cadherin loss promotes experimental metastasis of squamous cell carcinoma. European journal of cancer, Vol. 49, H. 8. pp. 2048-2058.

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Official URL: http://edoc.unibas.ch/dok/A6164881

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T-cadherin is gaining recognition as a determinant for the development of incipient invasive squamous cell carcinoma (SCC). However, effects of T-cadherin expression on the metastatic potential of SCC have not been studied. Here, using a murine model of experimental metastasis following tail vein injection of A431 SCC cells we report that loss of T-cadherin increased both the incidence and rate of appearance of lung metastases. T-cadherin-silenced SCC metastases were highly disordered with evidence of single cell dissemination away from main foci whereas SCC metastases overexpressing T-cadherin developed as compact, tightly organised sheets. SCC cell adhesion to vascular endothelial cells (EC) in culture was increased for T-cadherin-silenced SCC and decreased for T-cadherin-overexpressing SCC. Confocal microscopy showed that T-cadherin-silenced SCC adherent on EC display an elongated morphology with long thin extensions and a high degree of intercalation within the EC monolayer, whereas SCC overexpressing T-cadherin formed poorly-spread multicellular aggregates that remain on the outer surface of the EC monolayer. T-cadherin-deficient SCC or human keratinocyte cells exhibited increased transendothelial migration in vitro which could be attenuated in the presence of EGFR inhibitor gefitinib. Our data suggest that loss of T-cadherin can increase metastatic potential and aggressiveness of SCC, possibly due to facilitating arrest and extravasation through the vascular wall and/or more efficient establishment of metastases in the new microenvironment.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
03 Faculty of Medicine > Departement Biomedizin > Further Research Groups at DBM > Signal Transduction (Resink/Erne)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunotherapy (Iezzi)
UniBasel Contributors:Resink, Thérèse J. and Spagnoli, Giulio C. and Iezzi, Giandomenica and Erne, Paul
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Pergamon Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Mar 2015 07:44
Deposited On:25 Oct 2013 08:33

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