Although studies have mentioned that ADAM family proteases can mediate ectodomain shedding of HB-EGF to activate EGFR signaling pathways [22,41], it is still unknown whether ADAM8 is implicated in EGFR activation in GBM under TMZ treatment, in this case by increasing the total amount of HB-EGF, so that shedding of HB-EGF is not the major function of ADAM8 (data not shown). Here, HBEGF is linked to glioblastoma.