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. 2019 Nov 15;22(5):625–638. doi: 10.1093/neuonc/noz214

Fig. 6.

Fig. 6

Targeting TAA necroptosis suppressed MB stemness and dissemination. (A) Immunoblotting analysis of RIP3, MLKL, and cleaved caspase-3 expression in TAA and MB cells within disseminated MB. (B) Representative images of RIP1, RIP3, and S100β expression in TAA. (C) Lysate from primary TAA (pTAA) and disseminated TAA (dTAA) immunoprecipitated with anti-RIP1 antibody and tested for expression of RIP1 and RIP3. Input control was probed. (D) Concentration of CCL2 in media of MTX-treated primary TAA following pretreatment of Nec-1 or DMSO (n = 3). Immunoblotting analysis of RIP1/RIP3/MLKL and cleaved caspase-3 expression in these TAA. (E) MB disseminations (white arrow) examined by microPET/CT. Ratio of SUV showing radioactive absorption of metastases (n = 3/group). (F) Tumor volumes of xenografts (red arrow) derived from primary MBSCs following treatment with Nec-1 plus MTX, MCT plus MTX or Nec-1 plus MCT examined by microMRI (n = 6/group). (G) Survival curve of xenograft-bearing mice in above-mentioned groups. (H) Immunoblotting analysis of RIP1/RIP3/MLKL and CCL2 expression in xenografts following treatment with Nec-1 plus MTX or MCT plus MTX. (I) The schematic model showing necroptosis-associated TAA cytokine microenvironment underlying MB recurrence or dissemination contributes to maintaining MBSC stemness via Notch signaling activation. Scale bars, 10 μm.