Multicopper oxidases (MCOs), such as ascorbic acid oxidase and ceruloplasmin,are multidomain proteins capable of oxidizing many structurally unrelated compoundsreducing oxygen to water without ever generating reactive oxygen species. WhileMCOs show great oxidative versatility, they can only transfer electrons to molecularoxygen, which is the obligate electron acceptor. Therefore, MCOs could also be consideredas ''O2 consuming enzymes'', thus contributing to create those states of hypoxia that arenormally found in tissues, cells and cell compartments. Since hypoxia is also a commonfeature of many rapidly growing solid tumors, we postulate that the regulation ofGPI-ceruloplasmin isoform, present on the surface of the plasma membrane, could bethe molecular event in the creation and the maintenance of hypoxia in tumor cells.By silencing the different MCO genes with siRNA, it would appear possible to attempt toovercome tumor hypoxia, thus improving the efficiency of radiotherapy.

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, wepostulate 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.