Microglial-stimulation of glioma invasion involves the EGFR ligand amphiregulin

Autor: Jeffrey E. Segall, Salvatore J. Coniglio
Rok vydání: 2021
Předmět:
MAPK/ERK pathway
Cancer Treatment
Biochemistry
Mice
White Blood Cells
RNA interference
Animal Cells
Breast Tumors
Medicine and Health Sciences
Neurological Tumors
Cultured Tumor Cells
Multidisciplinary
Microglia
Chemistry
Brain Neoplasms
Glioma
Small interfering RNA
Up-Regulation
ErbB Receptors
Gene Expression Regulation
Neoplastic
Nucleic acids
medicine.anatomical_structure
Oncology
Neurology
Medicine
Biological Cultures
Signal transduction
Cellular Types
Signal Transduction
Research Article
Science
Immune Cells
Immunology
Glial Cells
Research and Analysis Methods
Amphiregulin
Malignant Tumors
Downregulation and upregulation
Cell Line
Tumor
Breast Cancer
medicine
Genetics
Animals
Humans
Neoplasm Invasiveness
Non-coding RNA
Microglial Cells
Blood Cells
Macrophages
Biology and Life Sciences
Cancers and Neoplasms
Cell Biology
Cell Cultures
medicine.disease
Glioma Cells
Gene regulation
Mice
Inbred C57BL
Cell culture
Cancer research
RNA
Gene expression
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 11, p e0260252 (2021)
ISSN: 1932-6203
Popis: High grade glioma is one of the deadliest human cancers with a median survival rate of only one year following diagnosis. The highly motile and invasive nature of high grade glioma makes it difficult to completely remove surgically. Therefore, increasing our knowledge of the mechanisms glioma cells use to invade normal brain is of critical importance in designing novel therapies. It was previously shown by our laboratory that tumor-associated microglia (TAMs) stimulate glioma cell invasion and this process is dependent on CSF-1R signaling. In this study, we seek to identify pro-invasive factors that are upregulated in microglia in a CSF-1R-dependent manner. We assayed cDNA and protein from microglia treated with conditioned media from the murine glioma cell line GL261, and discovered that several EGFR ligands including amphiregulin (AREG) are strongly upregulated. This upregulation is blocked by addition of a pharmacological CSF-1R inhibitor. Using RNA interference, we show that AREG-depleted microglia are less effective at promoting invasion of GL261 cells into Matrigel-coated invasion chambers. In addition, an AREG blocking antibody strongly attenuates the ability of THP-1 macrophages to activate human glioma cell line U87 invasion. Furthermore, we have identified a signaling pathway which involves CSF-1 signaling through ERK to upregulate AREG expression in microglia. Interfering with ERK using pharmacological inhibitors prevents AREG upregulation in microglia and microglia-stimulated GL261 invasion. These data highlight AREG as a key factor in produced by tumor associated microglia in promoting glioma invasion.
Databáze: OpenAIRE
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