[abstract] OXYGEN-REGULATED VEGF LEVELS IN OVARIAN CANCER CELLS.

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[abstract] OXYGEN-REGULATED VEGF LEVELS IN OVARIAN CANCER CELLS.

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Title: [abstract] OXYGEN-REGULATED VEGF LEVELS IN OVARIAN CANCER CELLS.
Author: Vuk-Pavlovic, S; Knutson, GJ
Abstract: BACKGROUND: Human tumor cells cultured at pO2=20 kPa are tested as whole-cell vaccines for tumor immunotherapy, but their relevance for hypoxic tumors in situ and their responsiveness to hyperbaric oxygen therapy are unclear. To determine if ovarian cancer (OvCa) cells respond to hypoxia and hyperoxia, we studied the expression of vascular endothelial growth factor (VEGF), a hallmark of OvCa, as a function of pO2. MATERIALS AND METHODS: We grew human OvCa cells OV17, OV167 or OV207 for three days in 20% fetal bovine serum at pO2=20 kPa until 80% confluent. Then we cultured them at pO2=1 kPa, 20 kPa or 90 kPa for up to 72 h while quantifying proliferation and secreted VEGF121+VEGF165 by ELISA and intracellular hypoxia-inducible factor 1 (HIF-1) by Western blotting. RESULTS: VEGF concentration increased with time in the media of OvCa cells at all pO2 values (p<0.01). While normoxic cells doubled twice over three days, VEGF secretion per cell per hour dropped (p=0.02). Hypoxia enhanced the rate of VEGF secretion in all cells. Hyperoxia abolished proliferation (p=0.0008), but unexpectedly boosted VEGF secretion (p=0.0258). We compared HIF-1 levels in normoxic cells and cells cultured in hypoxia or hyperoxia for 18 to 24 hours; HIF-1 levels in hypoxic cells were higher than in normoxic. Interestingly, hyperoxic cells also expressed high HIF-1 levels paralleling high VEGF secretion. CONCLUSIONS: Adherent OvCa cells respond both to hypoxia and hyperoxia by elevated levels of HIF-1 and VEGF. As this elevation was prominent in subconfluent growth-arrested hyperoxic cells, it is possible that proliferation and/or contact inhibition diminish HIF-1 levels. These findings support the hypothesis that whole-cell vaccines should be prepared under pO2 akin to that in situ. The findings of high HIF-1 levels in hyperoxic and subconfluent cells necessitate further studies of the underlying mechanism of HIF-1 stabilization.
Description: Abstract of the Undersea and Hyperbaric Medical Society, Inc. Annual Scientific Meeting held June 14-16, 2007. Ritz-Carlton Kapalua Maui, Hawaii (http:www.uhms.org)
URI: http://archive.rubicon-foundation.org/5213
Date: 2007

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  • UHMS Meeting Abstracts
    This is a collection of the published abstracts from the Undersea and Hyperbaric Medical Society (UHMS) annual meetings.

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