title: Activation of toll-like receptor 2 promotes invasion by upregulating MMPs in glioma stem cells.
abstract: Invasion is one of the deadly characteristics of malignant glioma with unknown underlying cellular and molecular mechanisms. In the present study, we investigated the role of toll-like receptor 2 (TLR2) in the invasiveness of malignant glioma. We enriched glioma stem cells (GSCs) from mouse GL261 cell line by means of tumor sphere formation, and found that GSCs expressed a significantly higher level of TLR2 than committed GL261 cells at the levels of mRNA and protein. Stimulation with Pam3CSK4, a ligand of TLR2, significantly increased the migration and invasion capability of GSCs. Knockdown of TLR2 attenuated the stimulating effect of Pam3CSK4 and the invasion capability of GSCs. An orthotopic allograft tumor model showed that TLR2-knockdown decreased the invasion capability of GSCs and prolonged survival span of tumor-bearing mice. The expressions of matrix metalloproteinases 2, 9 (MMP2 and MMP9) by GSCs were enhanced by treatment of Pam3CSK4 and decreased by TLR2 knockdown, implying that MMP2 and MMP9 were involved in TLR2-mediated invasion of GSCs. Our findings indicate that the activation of TLR2 up-regulates MMPs to promote invasion of GSCs, and suggest that TLR2 might be a potential therapeutic target for treatment of glioma patients.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Ye
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Cui
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University Chongqing, China.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
keywords: Glioma stem cells; Pam3CSK4; invasion; matrix metalloproteinases; toll-like receptor 2