Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion

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Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. / Markovic, D S; Vinnakota, K; Chirasani, S; Synowitz, M; Raguet, H; Stock, K; Sliwa, M; Lehmann, S; Kälin, R; van Rooijen, N; Holmbeck, K; Heppner, F L; Kiwit, J; Matyash, V; Lehnardt, S; Kaminska, B; Glass, R; Kettenmann, H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 30, 28.07.2009, p. 12530-5.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Markovic, DS, Vinnakota, K, Chirasani, S, Synowitz, M, Raguet, H, Stock, K, Sliwa, M, Lehmann, S, Kälin, R, van Rooijen, N, Holmbeck, K, Heppner, FL, Kiwit, J, Matyash, V, Lehnardt, S, Kaminska, B, Glass, R & Kettenmann, H 2009, 'Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 30, pp. 12530-5. https://doi.org/10.1073/pnas.0804273106

APA

Markovic, D. S., Vinnakota, K., Chirasani, S., Synowitz, M., Raguet, H., Stock, K., Sliwa, M., Lehmann, S., Kälin, R., van Rooijen, N., Holmbeck, K., Heppner, F. L., Kiwit, J., Matyash, V., Lehnardt, S., Kaminska, B., Glass, R., & Kettenmann, H. (2009). Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proceedings of the National Academy of Sciences of the United States of America, 106(30), 12530-5. https://doi.org/10.1073/pnas.0804273106

Vancouver

Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proceedings of the National Academy of Sciences of the United States of America. 2009 Jul 28;106(30):12530-5. https://doi.org/10.1073/pnas.0804273106

Author

Markovic, D S ; Vinnakota, K ; Chirasani, S ; Synowitz, M ; Raguet, H ; Stock, K ; Sliwa, M ; Lehmann, S ; Kälin, R ; van Rooijen, N ; Holmbeck, K ; Heppner, F L ; Kiwit, J ; Matyash, V ; Lehnardt, S ; Kaminska, B ; Glass, R ; Kettenmann, H. / Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 30. pp. 12530-5.

Bibtex

@article{172cd27fbdd644efa2f1b78300d46ff6,
title = "Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion",
abstract = "Diffuse infiltration of glioma cells into normal brain tissue is considered to be a main reason for the unfavorable outcomes of patients with malignant gliomas. Invasion of glioma cells into the brain parenchyma is facilitated by metalloprotease-mediated degradation of the extracellular matrix. Metalloproteases are released as inactive pro-forms and get activated upon cleavage by membrane bound metalloproteases. Here, we show that membrane type 1 metalloprotease (MT1-MMP) is up-regulated in glioma-associated microglia, but not in the glioma cells. Overexpression of MT1-MMP is even lethal for glioma cells. Glioma-released factors trigger the expression and activity of MT1-MMP via microglial toll-like receptors and the p38 MAPK pathway, as deletion of the toll-like receptor adapter protein MyD88 or p38 inhibition prevented MT1-MMP expression and activity in cultured microglial cells. Microglial MT1-MMP in turn activates glioma-derived pro-MMP-2 and promotes glioma expansion, as shown in an ex vivo model using MT1-MMP-deficient brain tissue and a microglia depletion paradigm. Finally, MyD88 deficiency or microglia depletion largely attenuated glioma expansion in 2 independent in vivo models.",
keywords = "Animals, Blotting, Western, Brain Neoplasms/genetics, Cell Line, Tumor, Enzyme Precursors/metabolism, Female, Gelatinases/metabolism, Gene Expression Regulation, Neoplastic, Glioma/genetics, Green Fluorescent Proteins/genetics, Humans, Immunohistochemistry, Male, Matrix Metalloproteinase 14/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia/metabolism, Myeloid Differentiation Factor 88/genetics, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Toll-Like Receptors/metabolism, Tumor Burden, p38 Mitogen-Activated Protein Kinases/metabolism",
author = "Markovic, {D S} and K Vinnakota and S Chirasani and M Synowitz and H Raguet and K Stock and M Sliwa and S Lehmann and R K{\"a}lin and {van Rooijen}, N and K Holmbeck and Heppner, {F L} and J Kiwit and V Matyash and S Lehnardt and B Kaminska and R Glass and H Kettenmann",
year = "2009",
month = jul,
day = "28",
doi = "10.1073/pnas.0804273106",
language = "English",
volume = "106",
pages = "12530--5",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "30",

}

RIS

TY - JOUR

T1 - Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion

AU - Markovic, D S

AU - Vinnakota, K

AU - Chirasani, S

AU - Synowitz, M

AU - Raguet, H

AU - Stock, K

AU - Sliwa, M

AU - Lehmann, S

AU - Kälin, R

AU - van Rooijen, N

AU - Holmbeck, K

AU - Heppner, F L

AU - Kiwit, J

AU - Matyash, V

AU - Lehnardt, S

AU - Kaminska, B

AU - Glass, R

AU - Kettenmann, H

PY - 2009/7/28

Y1 - 2009/7/28

N2 - Diffuse infiltration of glioma cells into normal brain tissue is considered to be a main reason for the unfavorable outcomes of patients with malignant gliomas. Invasion of glioma cells into the brain parenchyma is facilitated by metalloprotease-mediated degradation of the extracellular matrix. Metalloproteases are released as inactive pro-forms and get activated upon cleavage by membrane bound metalloproteases. Here, we show that membrane type 1 metalloprotease (MT1-MMP) is up-regulated in glioma-associated microglia, but not in the glioma cells. Overexpression of MT1-MMP is even lethal for glioma cells. Glioma-released factors trigger the expression and activity of MT1-MMP via microglial toll-like receptors and the p38 MAPK pathway, as deletion of the toll-like receptor adapter protein MyD88 or p38 inhibition prevented MT1-MMP expression and activity in cultured microglial cells. Microglial MT1-MMP in turn activates glioma-derived pro-MMP-2 and promotes glioma expansion, as shown in an ex vivo model using MT1-MMP-deficient brain tissue and a microglia depletion paradigm. Finally, MyD88 deficiency or microglia depletion largely attenuated glioma expansion in 2 independent in vivo models.

AB - Diffuse infiltration of glioma cells into normal brain tissue is considered to be a main reason for the unfavorable outcomes of patients with malignant gliomas. Invasion of glioma cells into the brain parenchyma is facilitated by metalloprotease-mediated degradation of the extracellular matrix. Metalloproteases are released as inactive pro-forms and get activated upon cleavage by membrane bound metalloproteases. Here, we show that membrane type 1 metalloprotease (MT1-MMP) is up-regulated in glioma-associated microglia, but not in the glioma cells. Overexpression of MT1-MMP is even lethal for glioma cells. Glioma-released factors trigger the expression and activity of MT1-MMP via microglial toll-like receptors and the p38 MAPK pathway, as deletion of the toll-like receptor adapter protein MyD88 or p38 inhibition prevented MT1-MMP expression and activity in cultured microglial cells. Microglial MT1-MMP in turn activates glioma-derived pro-MMP-2 and promotes glioma expansion, as shown in an ex vivo model using MT1-MMP-deficient brain tissue and a microglia depletion paradigm. Finally, MyD88 deficiency or microglia depletion largely attenuated glioma expansion in 2 independent in vivo models.

KW - Animals

KW - Blotting, Western

KW - Brain Neoplasms/genetics

KW - Cell Line, Tumor

KW - Enzyme Precursors/metabolism

KW - Female

KW - Gelatinases/metabolism

KW - Gene Expression Regulation, Neoplastic

KW - Glioma/genetics

KW - Green Fluorescent Proteins/genetics

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Matrix Metalloproteinase 14/genetics

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Microglia/metabolism

KW - Myeloid Differentiation Factor 88/genetics

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Toll-Like Receptors/metabolism

KW - Tumor Burden

KW - p38 Mitogen-Activated Protein Kinases/metabolism

U2 - 10.1073/pnas.0804273106

DO - 10.1073/pnas.0804273106

M3 - Journal article

C2 - 19617536

VL - 106

SP - 12530

EP - 12535

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 30

ER -

ID: 201165473