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

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 qRTPCR indicated upregulation of pro-angiogenic factors IL-8, VEGF, Ephrin A] 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 micro-environment, T-cadherin upregulation on endothelial cells may potentiate intratumoral angiogenesis.