Journal
CANCER LETTERS
Volume 272, Issue 2, Pages 345-354Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.07.012
Keywords
Matrix detachment model; Necrosis; Anoikis; Melanoma
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Funding
- German-Israeli Foundation [817/2004]
- Israel Science Foundation [573/03]
- Israeli Ministry of Health
- Chief Scientist Office
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Anchorage-independence is a hallmark of invasive cancer. The setback of the classical poly-HEMA static matrix detachment (SMD) anoikis model is the absence of dynamic fluid circulation, resulting in cell aggregates. We addressed this problem by developing a novel 3D cell culture dynamic matrix detachment (DMD) model with a turbulent-free laminar flow, yielding a very low shear stress. In this study, we focused on melanoma cells where apoptosis was evaluated both via annexin V flow cytometry and caspase cleavage. The DMD model was superior to SMD in the induction of melanoma cell death and in revealing a shift from apoptosis to necrotic cell death, as evident by failure to activate caspase 9 and a decrease in annexin V stain. Combination of DMD with cisplatin could further accentuate necrotic cell death in cisplatin-resistant melanoma cells. Thus, the DMD model may be a useful matrix deprivation model to identify necrotic vs. apoptotic cell death pathways. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
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