Dataset Information

Pericyte mediates the infiltration, migration, and polarization of macrophages by CD163/MCAM axis in glioblastoma.

ABSTRACT: Microenvironment cells (MCs) play a critical role in tumor proliferation, progression, and metastasis. However, it has not been adequately addressed whether MCs could be used as a reliable prognostic marker in glioblastoma (GBM). In the current study, the cell pair (CP) score was constructed in 1137 GBM samples based on the cell pair algorithm and Gaussian finite mixture model (GMM) and was verified in 73 GBM samples from the Xiangya cohort. CP score predicted GBM patients' survival and response to anti-PD-1 treatment with high sensitivity. Macrophage markers CD68 and CD163 were co-expressed with pericyte markers MCAM and MG2. Pericyte could mediate the infiltration, migration, and M2 type polarization of macrophages by MCAM. The CP score was a valuable tool for predicting survival outcomes and guiding immunotherapy for GBM patients. Cell pair pericyte/macrophage and gene pair CD163/MCAM were biologically significant in the tumor microenvironment of GBM.

SUBMITTER: Zhang H

PROVIDER: S-EPMC9460550 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Pericyte mediates the infiltration, migration, and polarization of macrophages by CD163/MCAM axis in glioblastoma.

Zhang Hao H Zhang Nan N Wu Wantao W Wang Zeyu Z Dai Ziyu Z Liang Xisong X Zhang Liyang L Peng Yun Y Luo Peng P Zhang Jian J Liu Zaoqu Z Cheng Quan Q Liu Zhixiong Z

iScience 20220810 9

Microenvironment cells (MCs) play a critical role in tumor proliferation, progression, and metastasis. However, it has not been adequately addressed whether MCs could be used as a reliable prognostic marker in glioblastoma (GBM). In the current study, the cell pair (CP) score was constructed in 1137 GBM samples based on the cell pair algorithm and Gaussian finite mixture model (GMM) and was verified in 73 GBM samples from the Xiangya cohort. CP score predicted GBM patients' survival and response ...[more]

PMID: 36093059

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Project description:Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during ischemia have remained elusive. Methods: A microsphere embolism-induced ischemia model was used to evaluate the expression of GPR124 following microsphere embolism. Immunocytochemistry and stochastic optical reconstruction microscopy imaging were used to assess the expression and distribution of GPR124 in human brain vascular pericytes (HBVPs) and after the treatment with 3-morpholino-sydnonimine (SIN-1) or oxygen-glucose deprivation (OGD). The effect of GPR124 knockdown or overexpression on HBVP migration was analyzed in vitro using wound healing assays and a microfluidic device. GPR124 loss-of-function studies were performed in HBVPs and HEK293 cells using CRISPR-Cas9-mediated gene deletion. Time-lapse imaging was used to assess dynamic changes in the formation of filopodia in an individual cell. Finally, to explore the functional domains required for GPR124 activity, deletion mutants were constructed for each of the N-terminal domains. Results: GPR124 expression was increased in pericytes following microsphere embolism. Morphological analysis showed localization of GPR124 to focal adhesions where GPR124 bound directly to the actin binding protein vinculin and upregulated Cdc42. SIN-1 or OGD treatment redistributed GPR124 to the leading edges of HBVPs where GPR124 signaling was required for pericyte filopodia formation and directional migration. Partial deletion of GPR124 domains decreased SIN-1-induced filopodia formation and cell migration. Conclusion: Taken together, our results provide the first evidence for a role of GPR124 in pericyte migration under ischemic conditions and suggest that GPR124 was essential for Cdc42 activation and filopodia formation.

Project description:BackgroundEndometriosis (EMs) is a common benign gynecological disease that affects approximately 10% of females of reproductive age. Endometriosis ectopic lesions could recruit macrophages, which in turn facilitates endometriosis progression. Several studies have indicated that CCL20 derived from macrophages activates the expression of CCR6 in several cells and induces cell proliferation and migration. However, the function of the CCL20/CCR6 axis in the interactions between macrophages and endometriotic stromal cells (ESCs) in EMs has yet to be elucidated.MethodsEctopic and normal endometrial tissues were collected from 35 ovarian endometriosis patients and 21 control participants for immunohistochemical staining. It was confirmed that macrophages secreted CCL20 to promote CCR6 activation of ESCs during co-culture by ELISA, qRT-PCR and western blot analysis. CCK8 and Edu assays were used to detect cell proliferation, and wound healing and Transwell assay were used to detect cell migration. Autophagic flux was detected by measuring the protein expression levels of LC3 and P62by western blot and analyzing the red/yellow puncta after ESCs were transfected with mRFP-GFP-LC3 double fluorescence adenovirus (Ad-LC3). Lysosomal function was tested by quantifying the fluorescent intensities of Lyso-tracker and Gal3 and activity of acid phosphatase. In addition, co-IP experiments verified the binding relationship between CCR6 and TFEB. Finally, the suppressive effect of CCL20-NAb on endometriosis lesions in vivo was demonstrated in mice models.ResultsWe demonstrated that macrophages secreted CCL20 to promote CCR6 activation of ESCs during co-culture, which further induced the proliferation and migration of ESCs. We observed that the CCL20/CCR6 axis impaired lysosomal function and then blocked the autolysosome degradation process of autophagic flux in ESCs. The combination of CCR6 and TFEB to inhibit TFEB nuclear translocation mediates the role of the CCL20/CCR6 axis in the above process. We also found that co-culture with ESCs upregulated the production and secretion of CCL20 by macrophages. The suppression effect of CCL20-NAb on endometriosis lesions in vivo was demonstrated in mice models.ConclusionsOur data indicate that macrophages block TFEB-mediated autolysosome degradation process of autophagic flux in ESCs via the CCL20/CCR6 axis, thereby promoting ESC proliferation and migration.

Dataset Information

Pericyte mediates the infiltration, migration, and polarization of macrophages by CD163/MCAM axis in glioblastoma.

Publications

Pericyte mediates the infiltration, migration, and polarization of macrophages by CD163/MCAM axis in glioblastoma.

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