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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2008) 32, 1199–1206 (Printed in Great Britain)
Bcl-2 and caspase-8 related anoikis resistance in human osteosarcoma MG-63 cells
Dingsheng Lin, Jie Feng and Weishan Chen*
Department of Orthopedics, Institute of Orthopaedic Research, 2nd Affiliated Hospital, Medical College, Zhejiang University, #88 Jiefang Road, Hangzhou 310009, PR China


Abstract

Detachment of adherent cells from extracellular matrix results in apoptosis, a process termed “anoikis”. Resistance to anoikis is implicated in the progression of many malignancies by facilitating the migration and eventual colonization of distant sites. Human kidney epithelial cells 293T, human osteoblast cells hFOB 1.19 and human osteosarcoma cells Saos-2 significantly underwent anoikis when adherence was prevented. But human osteosarcoma MG-63 cells were distinctly anoikis resistant when detached. They formed large aggregates and showed little apoptosis compared to the other cells. When MG-63 cells were in suspension, caspase-8, physically associated with death receptor was activated by cell–matrix detachment, whereas. Caspase-3 and caspase-9 were not activated. Translational level of Bcl-2 significantly increased in a time-dependent manner, but the level of β-catenin and PI3K did not. Caspase-8 participates in an anoikis-inducing process in MG-63 cells at an early time, and overexpression of Bcl-2 blocks activation of caspase-8 making MG-63 cells anoikis resistant.


Key words: Anoikis, Osteosarcoma, Bcl-2, Caspase-8, PI3K, β-catenin.

*Corresponding author. Tel.: +86 571 8776 7023.


Received 24 September 2007/9 April 2008; accepted 5 July 2008

doi:10.1016/j.cellbi.2008.07.002


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)