Onoda J M, Kantak S S, Piechocki M P, Awad W, Chea R, Liu B, Honn K V
Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan 48202.
Radiat Res. 1994 Dec;140(3):410-8.
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 IIb beta 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 IIb beta 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 hyper-fractionated 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.
低剂量伽马辐射刺激B16黑色素瘤细胞中调节转移潜能的表型特征的表达。在B16黑色素瘤细胞暴露于0.25至2.0 Gy的伽马辐射后，观察到整合素受体（αIIbβ3）表达的短暂增加。这种受体表达的增加导致肿瘤细胞在体外对纤连蛋白的粘附增强，并在体内增加实验诱导的转移。在本报告中，我们确定了12-脂氧合酶代谢产物12-HETE在辐射增强转移中的作用。在暴露于0.5 Gy伽马辐射后<5分钟，检测到B16黑色素瘤细胞中12-HETE的生物合成显著增加。然后我们确定，在用脂氧合酶抑制剂NDGA在照射前处理细胞后，辐射增强的αIIbβ3整合素表达以及B16黑色素瘤细胞在体外对纤连蛋白的粘附和体内转移均降低。这些发现表明，与分次或超分次放疗中使用的剂量相当的低剂量辐射，通过花生四烯酸的脂氧合酶代谢和整合素受体的表面表达的快速和短暂改变，增加了存活肿瘤细胞的转移潜能。
