Use of multicellular tumor spheroids to dissect endothelial cell–tumor cell interactions: A role for T-cadherin in tumor angiogenesis

Ghosh, Sourabh; Joshi, Manjunath B.; Ivanov, Danila; Feder-Mengus, Chantal; Spagnoli, Giulio C.; Martin, Ivan; Erne, Paul; Resink, Therese J.

doi:10.1016/j.febslet.2007.08.038

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Volume 581, Issue 23 , Pages 4523-4528, 18 September 2007

Use of multicellular tumor spheroids to dissect endothelial cell–tumor cell interactions: A role for T-cadherin in tumor angiogenesis

Edited by Veli-Pekka Lehto

Sourabh Ghosh
- ICFS, Departments of Surgery and Research, University Hospital, Basel, Switzerland
- These authors contributed equally.
Manjunath B. Joshi
- Department of Research, Laboratory for Signal Transduction, Basel University Hospital, Hebelstrasse 20, CH 4031 Basel, Switzerland
- These authors contributed equally.
Danila Ivanov
- Department of Research, Laboratory for Signal Transduction, Basel University Hospital, Hebelstrasse 20, CH 4031 Basel, Switzerland
Chantal Feder-Mengus
- ICFS, Departments of Surgery and Research, University Hospital, Basel, Switzerland
Giulio C. Spagnoli
- ICFS, Departments of Surgery and Research, University Hospital, Basel, Switzerland
Ivan Martin
- ICFS, Departments of Surgery and Research, University Hospital, Basel, Switzerland
Paul Erne
- Division of Cardiology, Kantonsspital, Luzern, Switzerland
Therese J. Resink
- Department of Research, Laboratory for Signal Transduction, Basel University Hospital, Hebelstrasse 20, CH 4031 Basel, Switzerland
- Corresponding author. Fax: +41 61 265 2350.

Received 13 August 2007; accepted 19 August 2007. published online 28 August 2007.

Abstract

This study addresses establishment of an “in vitro” melanoma angiogenesis model using multicellular tumor spheroids (MCTS) of differentiated (HBL) or undifferentiated (NA8) melanoma cell lines. DNA microarray assay and qRT-PCR indicated upregulation of pro-angiogenic factors IL-8, VEGF, Ephrin A1 and ANGPTL4 in NA8-MCTSs (vs. monolayers) whereas these were absent in MCTS and monolayer cultures of HBL. Upon co-culture with endothelial cell line HMEC-1 NA8-MCTS attract, whereas HBL-MCTS repulse, HMEC-1. Overexpression of T-cadherin in HMEC-1 leads to their increased invasion and network formation within NA8-MCTS. Given an appropriate angiogenic tumor microenvironment, T-cadherin upregulation on endothelial cells may potentiate intratumoral angiogenesis.

Abbreviations: MCTS, multicellular tumor spheroids, EC, endothelial cell, HMEC-1, human microvascular EC line, T-cad, T-cadherin, CTL, cytotoxic T lymphocytes