T-cadherin loss promotes experimental metastasis of squamous cell carcinoma

Philippova, Maria; Pfaff, Dennis; Kyriakakis, Emmanouil; Buechner, Stanislaw A.; Iezzi, Giandomenica; Spagnoli, Giulio C.; Schoenenberger, Andreas; Erne, Paul; Resink, Therese J. (2013). T-cadherin loss promotes experimental metastasis of squamous cell carcinoma. European journal of cancer, 49(8), pp. 2048-2058. Elsevier 10.1016/j.ejca.2012.12.026

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Geriatric Clinic

UniBE Contributor:

Schoenenberger, Andreas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0959-8049

Publisher:

Elsevier

Language:

English

Submitter:

Rebecca Rufer

Date Deposited:

12 Jun 2014 14:59

Last Modified:

11 Nov 2015 09:34

Publisher DOI:

10.1016/j.ejca.2012.12.026

PubMed ID:

23369463

BORIS DOI:

10.7892/boris.46431

URI:

https://boris.unibe.ch/id/eprint/46431

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