title: Use of multicellular tumor spheroids to dissect endothelial cell-tumor cell interactions: a role for T-cadherin in tumor angiogenesis.
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.
authors.affiliation: ICFS, Departments of Surgery and Research, University Hospital, Basel, Switzerland.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Manjunath B
authors.initials: MB
authors.lastname: Joshi
authors.forename: Danila
authors.initials: D
authors.lastname: Ivanov
authors.forename: Chantal
authors.initials: C
authors.lastname: Feder-Mengus
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.forename: Therese J
authors.initials: TJ
authors.lastname: Resink
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism*
chemical_list: D015820:Cadherins