American Association for Cancer Research
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Supplementary Figures 1-9 from MET Signaling Regulates Glioblastoma Stem Cells

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journal contribution
posted on 2023-03-30, 21:15 authored by Kyeung Min Joo, Juyoun Jin, Eunhee Kim, Kang Ho Kim, Yonghyun Kim, Bong Gu Kang, Youn-Jung Kang, Justin D. Lathia, Kwang Ho Cheong, Paul H. Song, Hyunggee Kim, Ho Jun Seol, Doo-Sik Kong, Jung-Il Lee, Jeremy N. Rich, Jeongwu Lee, Do-Hyun Nam

PDF file - 6.4MB, Figure S1: High MET mRNA expression in GBM specimens portends poor patient survival. Figure S2: Dual immunofluorescence of MET and GSC enrichment markers (CD133 and CD15) on the frozen sections of GBM specimens. Figure S3: HGF/MET signaling in GBMs. Figure S4: METhigh cells generated xenograft tumors consisting of both METhigh and METlow/- cells. Figure S5: Immunohistochemical analysis of HGF protein in orthotopic xenograft tumors derived of from GBM 578 (A and C) and 464 (B and D). Figure S6: Effects of MET blockade on cell survival and clonogenicity of GSCs. Figure S7: In vitro migration and invasion assays using GSCs with MET targeting. Figure S8: Immunohistochemical analysis using human nuclei-specific antibody on the sections of GBM xenografts. Figure S9: Limiting dilution sphere forming assay to determine the clonogenic potentials of 822 GSCs after treatments of radiation and SU11274



Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM. Here, we identified a distinct fraction of cells expressing a high level of MET in human primary GBM specimens that were preferentially localized in perivascular regions of human GBM biopsy tissues and were found to be highly clonogenic, tumorigenic, and resistant to radiation. Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs. Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target. Cancer Res; 72(15); 3828–38. ©2012 AACR.

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