However, as for the type of IGF-II signal provided in this context, it is worth mentioning that the predominant IGF-II form secreted by cancer cells is its high-molecular weight (big)-IGF-II form which escapes IGFBP-3 and SpI2-6 (IGF2R) binding [49,50] which can biologically differentiate the IGF-II paracrine versus autocrine signal. Here, IGFBP3 is linked to cancer.