IGFBP3 and neoplasm: Although it might be reasonable to expect that a tumor addicted to IGF-IR/IGFs or IR-A/IGF-2 circuits may favorably respond to IGF-blocking activity of IGFBP3, it should be considered that high levels of IGFs and IGFBP3 may switch the balance of the phospholipid rheostat in favor of SP1 by activating SphK1.