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Ezrin enhances survival of single metastatic osteosarcoma cells that reach the lung in an AKT‐independent manner
Author(s) -
Hong SungHyeok,
Ren Ling,
Khanna Chand
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.238.5
Subject(s) - ezrin , extravasation , apoptosis , protein kinase b , cancer research , osteosarcoma , medicine , lung , cell , biology , chemistry , pathology , biochemistry , genetics , cytoskeleton
To determine mechanisms of early metastatic advantage provided by ezrin, we examined adhesion, extravasation, and survival early after osteosarcoma (OS) cell arrival in the lung. We found no evidence ezrin‐dependent influences on tumor cell adherence. Confocal imaging of green tumor cells against a red fluorescent vascular map, demonstrated extravasation of both high and low ezrin expressing cells within 15 minutes of arrival in the lung. However, apoptotic rate in cells that expressed high ezrin was significantly lower than cells with low ezrin expression as early as 3 hours after the arrival of cells in the lung. These data suggest that the early metastatic survival associated with ezrin expression was the result of ezrin‐associated inhibition of apoptosis of tumor cells that had left the vasculature early after their arrival in the lung. To further examine mechanisms for this apoptosis we stably expressed an active Akt construct (actAkt) in the low ezrin cells. We found no rescue of the ezrin‐dependent single‐cell metastatic survival between actAkt clones (n = 4) and empty vector clones (n = 2). In addition, Akt inhibitor I/II did not induce apoptosis in the early time of survival novel ex vivo lung culture assay of metastasis. These data suggest that the Akt pathway is not responsible for the induction of apoptosis seen in low ezrin expressing OS cells early after their arrival in the lung.