We were unable to detect increased metastasis to the liver of Shb +/− insulinomas [15] and the discrepancy between those findings and the current may lie in the difference in the local angiogenic milieu, which is probably dependent on a multitude of factors in melanomas whereas RIP-Tag2 insulinomas are highly dependent on VEGF and FGF-2 [49]. Here, SHB is linked to melanoma.