The possible role of GPI-ceruloplasmin in hypoxia de novo creation and maintenance

Ceruloplasmin is a member of the multicopper oxidases family (MCOs), multidomain proteins capable of oxidizing many structurally unrelated compounds reducing oxygen to water. While MCOs show great oxidative versatility, they can only transfer electrons to molecular oxygen, which is the obligate electron acceptor. Therefore, MCOs should also be considered as ''O 2 consuming enzymes''. The glycosylphosphatidylinositol anchored ceruloplasmin (GPI-Cp) isoform present on the surface of the plasma membrane, does not seem to be involved in copper and iron metabolism. Since hypoxia is also a common feature of many rapidly growing solid tumors, we postulate that the regulation of GPI-Cp could be the molecular event in the creation and the maintenance of hypoxia in tumor cells. By inhibiting the GPI-Cp expression, it would appear possible to attempt to overcome tumor hypoxia, thus improving the efficiency of radiotherapy.