The Chemokine Receptor CCR1 Mediates Microglia Stimulated Glioma Invasion

被引:7
|
作者
Zeren, Nazende [1 ]
Afzal, Zobia [1 ]
Morgan, Sara [1 ]
Marshall, Gregory [1 ,3 ]
Uppiliappan, Maithrayee [1 ]
Merritt, James [1 ,4 ]
Coniglio, Salvatore J. J. [1 ,2 ]
机构
[1] Kean Univ, Sch Integrat Sci & Technol, Union, NJ 07083 USA
[2] Kean Univ, Dept Biol Sci, Union, NJ 07083 USA
[3] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA
[4] Genesis Biotechnol Grp, Hamilton, NJ 08691 USA
关键词
glioma; microglia; macrophage; invasion; CCR1; CCL3; CSF1R; COLORECTAL-CANCER PROGRESSION; MYELOID CELLS; FACTOR-1; RECEPTOR; GLIOBLASTOMA; ACCUMULATION; EXPRESSION; METASTASIS; MACROPHAGES; PROMOTE; TUMORS;
D O I
10.3390/ijms24065136
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glioblastoma multiforme (GBM) is the most aggressive form of adult brain tumor which is highly resistant to conventional treatment and therapy. Glioma cells are highly motile resulting in infiltrative tumors with poorly defined borders. Another hallmark of GBM is a high degree of tumor macrophage/microglia infiltration. The level of these tumor-associated macrophages/microglia (TAMs) correlates with higher malignancy and poorer prognosis. We previously demonstrated that inhibition of TAM infiltration into glioma tumors with the CSF-1R antagonist pexidartinib (PLX3397) can inhibit glioma cell invasion in-vitro and in-vivo. In this study, we demonstrate an important role for the chemokine receptor CCR1 in mediating microglia/TAM stimulated glioma invasion. Using two structurally distinct CCR1 antagonists, including a novel inhibitor "MG-1-5", we were able to block microglial activated GL261 glioma cell invasion in a dose dependent manner. Interestingly, treatment of a murine microglia cell line with glioma conditioned media resulted in a strong induction of CCR1 gene and protein expression. This induction was attenuated by inhibition of CSF-1R. In addition, glioma conditioned media treatment of microglia resulted in a rapid upregulation of gene expression of several CCR1 ligands including CCL3, CCL5, CCL6 and CCL9. These data support the existence of tumor stimulated autocrine loop within TAMs which ultimately mediates tumor cell invasion.
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页数:11
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