The multifactorial roles of microglia and macrophages in the maintenance and progression of glioblastoma

Chaudhary, Rishabh; Morris, Rhianna J.; Steinson, Emma

doi:10.1016/j.jneuroim.2021.577633

Cited by 18 publications

(15 citation statements)

References 317 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microglia appear to play an important role in glioma tumor progression by affecting the tissue microenvironment [ 8 , 34 ]. An important aspect of microglial function is the release of cytokines and factors that promote glioma cell proliferation and invasion [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Microglial Cytokines Induce Invasiveness and Proliferation of Human Glioblastoma through Pyk2 and FAK Activation

Nuñez

Valle

Ortiz

et al. 2021

Cancers

View full text Add to dashboard Cite

Glioblastoma is the most aggressive brain tumor in adults. Multiple lines of evidence suggest that microglia create a microenvironment favoring glioma invasion and proliferation. Our previous studies and literature reports indicated the involvement of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) in glioma cell proliferation and invasion, stimulated by tumor-infiltrating microglia. However, the specific microglia-released factors that modulate Pyk2 and FAK signaling in glioma cells are unknown. In this study, 20 human glioblastoma specimens were evaluated with the use of RT-PCR and western blotting. A Pierson correlation test demonstrated a correlation (0.6–1.0) between the gene expression levels for platelet-derived growth factor β(PDGFβ), stromal-derived factor 1α (SDF-1α), IL-6, IL-8, and epidermal growth factor (EGF) in tumor-purified microglia and levels of p-Pyk2 (Y579/Y580) and p-FAK(Y925) in glioma cells. siRNA knockdown against Pyk2 or FAK in three primary glioblastoma cell lines, developed from the investigated specimens, in combination with the cytokine receptor inhibitors gefitinib (1 μM), DMPQ (200 nM), and burixafor (1 μM) identified EGF, PDGFβ, and SDF-1α as key extracellular factors in the Pyk2- and FAK-dependent activation of invadopodia formation and the migration of glioma cells. EGF and IL-6 were identified as regulators of the Pyk2- and FAK-dependent activation of cell viability and mitosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Microglial Cytokines Induce Invasiveness and Proliferation of Human Glioblastoma through Pyk2 and FAK Activation

Nuñez

Valle

Ortiz

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…The CD163/IL‐6/Stat3 pathway is suggested to be critical in protumor TAMs, however, macrophage‐mediated cancer cell proliferation was not affected by anti‐IL‐6R antibody (unpublished data). Since it is well known that TAMs secrete many protumor factors, 32 unknown protumor factors derived macrophages might be involved in macrophage‐mediated hepatoblastoma cell growth.…”

Section: Discussionmentioning

confidence: 99%

IL‐34 in hepatoblastoma cells potentially promote tumor progression via autocrine and paracrine mechanisms

et al. 2022

View full text Add to dashboard Cite

Hepatoblastoma is the most common pediatric liver tumor, but little research has been done on the role of macrophages in hepatoblastoma. The purpose of this study was to gain insight into potential roles for macrophages in hepatoblastoma. Paraffin-embedded specimens from 56 patients who underwent surgical resection were examined with immunohistochemical staining for the macrophage-specific markers, Iba1 and CD163. Significant differences were seen among histological subtypes. Significantly increased numbers of macrophages were detected in embryonal components compared to fetal components in the mixed epithelial type. In vitro studies using human monocyte-derived macrophages and two hepatoblastoma cell lines (HepG2 and Huh6) were performed.Conditioned medium from these cell lines induced increased CD163 expression in macrophages. Direct co-culture with macrophages induced tumor cell proliferation via induction of protumor cytokine secretion from macrophages. Direct co-culture with macrophages also induced interleukin (IL)-34 overexpression by Huh6 cells via Brd4 signaling. IL-34 overexpression promoted tumor cell proliferation and chemoresistance. High IL-34 and Brd4 expression was detected in embryonal components, which have potentially higher proliferation activity than fetal components. In conclusion, IL-34 expression in embryonal components may induce macrophage chemotaxis in a paracrine manner, and tumor cell proliferation and chemoresistance in an autocrine manner. IL-34 is a potential therapeutic target for hepatoblastoma.

show abstract

“…Normal FA values range from 0.4 to 0.8 [40,41], and depend on the white matter architecture, i.e., the 3D organization of fascicles and the conservation of axonal membranes [42], and at a lesser extent on an MRI machine [43]. Thus, the core of the structural disorganization is maximal (highest ADC; lower FA) within the MV, where the necrosis developed, and which is surrounded by an intense immune reaction [44] and noticeably the angiogenesis identified on CT-Scan, MRI, and ultrasound [45,46]. In GBM, the diffusion decreased between MV and either BAT or aCCV, which had comparable mean ADC values likely because of the infiltrative nature of the lesion [16].…”

Section: Discussionmentioning

confidence: 99%

DTI Abnormalities Related to Glioblastoma: A Prospective Comparative Study with Metastasis and Healthy Subjects

et al. 2022

View full text Add to dashboard Cite

(1) Background: Glioblastoma multiforme (GBM) shows complex mechanisms of spreading of the tumor cells, up to remote areas, and little is still known of these mechanisms, thus we focused on MRI abnormalities observable in the tumor and the brain adjacent to the lesion, up to the contralateral hemisphere, with a special interest on tensor diffusion imaging informing on white matter architecture; (2) Material and Methods: volumes, macroscopic volume (MV), brain-adjacent-tumor (BAT) volume and abnormal color-coded DTI volume (aCCV), and region-of-interest samples (probe volumes, ipsi, and contra lateral to the lesion), with their MRI characteristics, apparent diffusion coefficient (ADC), fractional anisotropy (FA) values, and number of fibers (DTI fiber tracking) were analyzed in patients suffering GBM (n = 15) and metastasis (n = 9), and healthy subjects (n = 15), using ad hoc statistical methods (type I error = 5%) (3) Results: GBM volumes were larger than metastasis volumes, aCCV being larger in GBM and BAT ADC was higher in metastasis, ADC decreased centripetally in metastasis, FA increased centripetally either in GBM or metastasis, MV and BAT FA values were higher in GBM, ipsi FA values of GBM ROIs were higher than those of metastasis, and the GBM ipsi number of fibers was higher than the GBM contra number of fibers; (4) Conclusions: The MV, BAT and especially the aCCV, as well as their related water diffusion characteristics, could be useful biomarkers in oncology and functional oncology.

show abstract

The multifactorial roles of microglia and macrophages in the maintenance and progression of glioblastoma

Cited by 18 publications

References 317 publications

Microglial Cytokines Induce Invasiveness and Proliferation of Human Glioblastoma through Pyk2 and FAK Activation

Microglial Cytokines Induce Invasiveness and Proliferation of Human Glioblastoma through Pyk2 and FAK Activation

IL‐34 in hepatoblastoma cells potentially promote tumor progression via autocrine and paracrine mechanisms

DTI Abnormalities Related to Glioblastoma: A Prospective Comparative Study with Metastasis and Healthy Subjects

Contact Info

Product

Resources

About