T-cadherin loss promotes experimental metastasis of squamous cell carcinoma
Publisher DOI
PubMed ID
23369463
Abstract
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.
Date Issued
2013-05
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Philippova, Maria | |
Pfaff, Dennis | |
Kyriakakis, Emmanouil | |
Buechner, Stanislaw A. | |
Iezzi, Giandomenica | |
Spagnoli, Giulio C. | |
Erne, Paul | |
Resink, Therese J. |
Additional Credits
Journal
European journal of cancer
Publisher
Elsevier
ISSN
0959-8049
Access(Rights)
restricted