A novel dynamic matrix detachment model reveals a shift from apoptosis to necrosis in melanoma cells.

Abstract

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.

• Authors: Keren Tzukert, Raphael Gorodestky, Idit Avrahami, Lina Krasny, Nilly Shimony, Gregory Elkin, Dirk M Nettelbeck, Yosef S Haviv
• Journal: Cancer letters (Cancer Lett) Vol. 272 Issue 2 Pg. 345-54 (Dec 18 2008) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 18723276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Apoptosis
• Blotting, Western
• Cell Line, Tumor
• Flow Cytometry
• Melanoma, Experimental (pathology)
• Mice
• Models, Biological
• Necrosis