Human melanoma cells expressing the αvβ3 integrin are partially protected from necrotic cell death induced by dynamic matrix detachment

K. Tzukert, N. Shimony, L. Krasny, S. Urieli-Shoval, R. Gorodetsky, I. Avrahami, D. M. Nettelbeck, Y. S. Haviv

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Anchorage-independence is a hallmark of metastatic cancer cells. In previous studies we characterized a novel model for anchorage-independence employing dynamic matrix detachment (DMD) using rotation in low shear stress conditions. We observed that in contrast to the classical apoptosis-inducing static matrix detachment (SMD) model, the venous circulation-mimicking DMD model induced necrosis in transformed cells. In the current study we revisited the mechanism of DMD-induced cell death and evaluated the contribution of αvβ3 integrin overexpression in human melanoma cells to anchorage-independence in DMD. DMD cell culture induced primarily necrosis in the melanoma cells studied. αvβ3, but not the control related αIIbβ3 integrin, could confer survival advantage in DMD. While apoptosis was unaffected, constitutive, unligated αvβ3 overexpression was associated with attenuation of necrosis in DMD. αvβ3 overexpressing melanoma cells manifested AKT activation that was independent of DMD conditions. Furthermore, while a small molecular inhibitor of AKT phosphorylation induced apoptosis in adherent cells, in DMD conditions it had no effect on cell outcome. Thus, αvβ3-overexpressing melanoma cells are partially protected from DMD-induced cell death in an apoptosis-independent mechanism. This finding may be one of the factors accounting for anchorage-independence in circulating metastatic melanoma cells.

Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalCancer Letters
Volume290
Issue number2
DOIs
StatePublished - 28 Apr 2010
Externally publishedYes

Keywords

  • Anchorage-independence
  • Apoptosis
  • Dynamic matrix detachment
  • Melanoma
  • Necrosis
  • αvβ3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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