Inhibition of radiation-enhanced expression of integrin and metastatic potential in B16 melanoma cells by a lipoxygenase inhibitor
- Wayne State Univ. School of Medicine, Detroit, MI (United States)
Low-dose {gamma} radiation stimulates expression of phenotypic characteristics in B16 melanoma cells which regulate metastatic potential. A transient increase in the expression of an integrin receptor ({alpha}{sub IIb}{beta}{sub 3}) was observed after exposure of B16 melanoma cells to 0.25 to 2.0 Gy of {gamma} radiation. This increased receptor expression resulted in enhanced adhesion of tumor cells to fibronectin in vitro and increased experimentally induced metastasis in vivo. In this report, we determined a role for the 12-lipoxygenase metabolite, 12-HETE, in radiation-enhanced metastasis. A significant increase in biosynthesis of 12-HETE in B16 melanoma cells was detected <5 min after exposure to 0.5 Gy {gamma} radiation. We then determined that radiation-enhanced expression of {alpha}{sub IIb}{beta}{sub 3} integrin and adhesion of B16 melanoma cells to fibronectin in vitro and metastasis in vivo were reduced by treatment of the cells with the lipoxygenase inhibitor NDGA prior to irradiation. These findings suggest that low-dose radiation, at levels comparable to those used in fractionated or hyperfractionated radiotherapy, increases the metastatic potential of surviving tumor cells via a rapid and transient alteration in lipoxygenase metabolism of arachidonic acid and surface expression of an integrin receptor. 30 refs., 5 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 50633
- Journal Information:
- Radiation Research, Journal Name: Radiation Research Journal Issue: 3 Vol. 140; ISSN 0033-7587; ISSN RAREAE
- Country of Publication:
- United States
- Language:
- English
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