Heterogeneity among RIP-Tag2 insulinomas allows vascular endothelial growth factor-A independent tumor expansion as revealed by studies in Shb mutant mice: Implications for tumor angiogenesis

► Shb is an adapter protein operating downstream of VEGFR-2. ► Shb was presently investigated in the context of RIP-Tag2 angiogenesis. ► Absence of Shb reduces RIP-Tag2 tumor burden and VEGF-dependent tumor angiogenesis. ► A fraction of tumors escape the angiogenic inhibition imposed by the absence of Shb. ► Tumor heterogeneity allows escape from angiogenic restriction by various means.