This processing defect increases the life-span and bioavailability of the IGF-II variants, both in the tumor microenvironment and in the systemic circulation, by reducing binding to IGFBP-3 and the IGF-II scavenger protein SpI2-6 (deceivingly known as the IGF-II “receptor” but actually causing IGF-II sequestration and degradation) [10,11,12]. Here, IGF2 is linked to neoplasm.