Hypoxia increases adhesion and spreading of MG-63 three-dimensional tumor spheroids.
The effects of hypoxia on adhesion and spreading of MG-63 human osteosarcoma spheroids were investigated. Hypoxia was induced in 2-day-old, small spheroids and verified by HIF-1alpha expression. Changes in adhesion were examined on both tissue culture plates and plates coated with fibronectin or collagen while spreading was analyzed in cocultures of MG-63 spheroids seeded on primary fibroblasts grown as a monolayer. In order to better distinguish the two different cell types, MG-63 cells were previously stably transfected with the green fluorescent protein EGFP-vector. Changes in the expression of molecules involved in tumor adhesion and spreading, such as two key integrins (fibronectin receptor, alpha5, and collagen receptor, alpha2) and fibronectin were also examined. The results indicate that hypoxia increases adhesion of spheroids and enhances their ability to spread into the surrounding fibroblast cell culture. These changes in adhesion and spreading are accompanied by concomitant variations in the expression of alpha5 and alpha2 integrins and fibronectin.
Indovina
Paola
P
Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Roma, Italia.
Rainaldi
Gabriella
G
Santini
Maria Teresa
MT
D002448:Cell Adhesion; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D039081:Integrin alpha5beta1; D016023:Integrins; D012516:Osteosarcoma / Q000473:pathology; D038981:Receptors, Collagen; D018874:Spheroids, Cellular / Q000473:pathology*; D046509:Tissue Culture Techniques; D014162:Transfection
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D039081:Integrin alpha5beta1; D016023:Integrins; D038981:Receptors, Collagen; D003035:Cobalt; C018021:cobaltous chloride