Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

Stephanie Ghislin1, Dorian Obino1, Sandrine Middendorp1, Nicole Boggetto2, Catherine Alcaide-Loridan1 and Frederique Deshayes13*

Author affiliations

1 Team « Regulation des Reponses Immunitaires ». Institut Jacques Monod, CNRS, UMR 7592, Univ Paris Diderot, Sorbonne Paris Cité, Paris, F-75205, France

2 Imagoseine, plate-forme de cytometrie en flux, Institut Jacques Monod CNRS-Universite Paris Diderot, Paris, France

3 Equipe : « Regulation des Reponses Immunitaires», INSTITUT JACQUES MONOD, CNRS-Université Paris Diderot, Bâtiment Buffon. 15 rue Hélène Brion, Paris, 75205 PARIS CEDEX 13, France

For all author emails, please log on.

Citation and License

BMC Cancer 2012, 12:455  doi:10.1186/1471-2407-12-455

Published: 5 October 2012

Abstract

Background

Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration.

Methods

A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software.

Results

We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration.

Conclusion

Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration.

Keywords:
Melanoma; Transendothelial migration; Metastasis; LFA-1; ICAM-1; HUVEC