ADAM8 affects glioblastoma progression by regulating osteopontin-mediated angiogenesis
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ADAM8 affects glioblastoma progression by regulating osteopontin-mediated angiogenesis. / Li, Yu; Guo, Songbo; Zhao, Kai; Conrad, Catharina; Driescher, Caroline; Rothbart, Vanessa; Schlomann, Uwe; Guerreiro, Helena; Bopp, Miriam H; König, Alexander; Carl, Barbara; Pagenstecher, Axel; Nimsky, Christopher; Bartsch, Jörg W.
In: BIOL CHEM, Vol. 402, No. 2, 01.2021, p. 195-206.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - ADAM8 affects glioblastoma progression by regulating osteopontin-mediated angiogenesis
AU - Li, Yu
AU - Guo, Songbo
AU - Zhao, Kai
AU - Conrad, Catharina
AU - Driescher, Caroline
AU - Rothbart, Vanessa
AU - Schlomann, Uwe
AU - Guerreiro, Helena
AU - Bopp, Miriam H
AU - König, Alexander
AU - Carl, Barbara
AU - Pagenstecher, Axel
AU - Nimsky, Christopher
AU - Bartsch, Jörg W
PY - 2021/1
Y1 - 2021/1
N2 - Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a median survival of only 15 months. To complement standard treatments including surgery, radiation and chemotherapy, it is essential to understand the contribution of the GBM tumor microenvironment. Brain macrophages and microglia particularly contribute to tumor angiogenesis, a major hallmark of GBM. ADAM8, a metalloprotease-disintegrin strongly expressed in tumor cells and associated immune cells of GBMs, is related to angiogenesis and correlates with poor clinical prognosis. However, the specific contribution of ADAM8 to GBM tumorigenesis remains elusive. Knockdown of ADAM8 in U87 glioma cells led to significantly decreased angiogenesis and tumor volumes of these cells after stereotactic injection into striate body of mice. We found that the angiogenic potential of ADAM8 in GBM cells and in primary macrophages is mediated by the regulation of osteopontin (OPN), an important inducer of tumor angiogenesis. By in vitro cell signaling analyses, we demonstrate that ADAM8 regulates OPN via JAK/STAT3 pathway in U87 cells and in primary macrophages. As ADAM8 is a dispensable protease for physiological homeostasis, we conclude that ADAM8 could be a tractable target to modulate angiogenesis in GBM with minor side-effects.
AB - Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a median survival of only 15 months. To complement standard treatments including surgery, radiation and chemotherapy, it is essential to understand the contribution of the GBM tumor microenvironment. Brain macrophages and microglia particularly contribute to tumor angiogenesis, a major hallmark of GBM. ADAM8, a metalloprotease-disintegrin strongly expressed in tumor cells and associated immune cells of GBMs, is related to angiogenesis and correlates with poor clinical prognosis. However, the specific contribution of ADAM8 to GBM tumorigenesis remains elusive. Knockdown of ADAM8 in U87 glioma cells led to significantly decreased angiogenesis and tumor volumes of these cells after stereotactic injection into striate body of mice. We found that the angiogenic potential of ADAM8 in GBM cells and in primary macrophages is mediated by the regulation of osteopontin (OPN), an important inducer of tumor angiogenesis. By in vitro cell signaling analyses, we demonstrate that ADAM8 regulates OPN via JAK/STAT3 pathway in U87 cells and in primary macrophages. As ADAM8 is a dispensable protease for physiological homeostasis, we conclude that ADAM8 could be a tractable target to modulate angiogenesis in GBM with minor side-effects.
U2 - 10.1515/hsz-2020-0184
DO - 10.1515/hsz-2020-0184
M3 - SCORING: Journal article
C2 - 32845856
VL - 402
SP - 195
EP - 206
JO - BIOL CHEM
JF - BIOL CHEM
SN - 1431-6730
IS - 2
ER -
