Glioblastoma drives protease-independent extracellular matrix invasion of microglia
Glioblastoma (GBM) is the most common and lethal form of primary brain cancer. Microglia infiltration into the tumor microenvironment is associated with immunosuppression and poor prognosis. Improved physicochemical understanding of microglia activation and invasion may provide novel GBM therapeutic...
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Elsevier
2025-04-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S259000642500033X |
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| author | Chia-Wen Chang Ashwin Bale Rohit Bhargava Brendan A.C. Harley |
| author_facet | Chia-Wen Chang Ashwin Bale Rohit Bhargava Brendan A.C. Harley |
| author_sort | Chia-Wen Chang |
| collection | DOAJ |
| description | Glioblastoma (GBM) is the most common and lethal form of primary brain cancer. Microglia infiltration into the tumor microenvironment is associated with immunosuppression and poor prognosis. Improved physicochemical understanding of microglia activation and invasion may provide novel GBM therapeutic strategies essential for improving long-term treatment efficacy. Here, we combine microfluidic systems with 3-D collagen hydrogels to systematically investigate microglia activation, invasion, contractility and cytokine secretion in response to GBM-microglia crosstalk. GBM inflammatory biomolecules significantly promote activation and 3D invasion of microglia. Interestingly, microglia invasion is not significantly affected by inhibitors of MMP activity or cellular glycolysis. In contrast, ROCK-pathway inhibition significantly impedes microglia invasion. Infrared microscopy analyses show that GBM conditioned media does not significantly alter microglia lipid content. Further, GBM conditioned media resulted in significantly increased collagen hydrogel contraction, suggesting the importance of microglia contractility to physically remodel the local extracellular matrix (ECM). We also identify a panel of soluble proteins that may contribute to microglia chemotaxis, such as TIMP-1 and CXCL12. Taken together, this study suggests that the presence of GBM cells can enhance microglia invasion via increased cellular contractility, independent of MMP activity and cellular glycolysis. |
| format | Article |
| id | doaj-art-35bc5ce38c3c4f1c92c2cbd98df9da95 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-35bc5ce38c3c4f1c92c2cbd98df9da952025-01-18T05:05:07ZengElsevierMaterials Today Bio2590-00642025-04-0131101475Glioblastoma drives protease-independent extracellular matrix invasion of microgliaChia-Wen Chang0Ashwin Bale1Rohit Bhargava2Brendan A.C. Harley3Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Electrical and Computer Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; CZ Biohub Chicago, LLC, Chicago, IL 60642, USACarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Corresponding author. B.A.C. Harley Department of Chemical and Biomolecular Engineering Cancer Center at Illinois Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 110 Roger Adams Laboratory, 600 S. Mathews Ave., Urbana, IL 61801, USA.Glioblastoma (GBM) is the most common and lethal form of primary brain cancer. Microglia infiltration into the tumor microenvironment is associated with immunosuppression and poor prognosis. Improved physicochemical understanding of microglia activation and invasion may provide novel GBM therapeutic strategies essential for improving long-term treatment efficacy. Here, we combine microfluidic systems with 3-D collagen hydrogels to systematically investigate microglia activation, invasion, contractility and cytokine secretion in response to GBM-microglia crosstalk. GBM inflammatory biomolecules significantly promote activation and 3D invasion of microglia. Interestingly, microglia invasion is not significantly affected by inhibitors of MMP activity or cellular glycolysis. In contrast, ROCK-pathway inhibition significantly impedes microglia invasion. Infrared microscopy analyses show that GBM conditioned media does not significantly alter microglia lipid content. Further, GBM conditioned media resulted in significantly increased collagen hydrogel contraction, suggesting the importance of microglia contractility to physically remodel the local extracellular matrix (ECM). We also identify a panel of soluble proteins that may contribute to microglia chemotaxis, such as TIMP-1 and CXCL12. Taken together, this study suggests that the presence of GBM cells can enhance microglia invasion via increased cellular contractility, independent of MMP activity and cellular glycolysis.http://www.sciencedirect.com/science/article/pii/S259000642500033XBrain cancerImmune infiltrationExtracellular matrixContractilityMatrix degradationMicrofluidic |
| spellingShingle | Chia-Wen Chang Ashwin Bale Rohit Bhargava Brendan A.C. Harley Glioblastoma drives protease-independent extracellular matrix invasion of microglia Materials Today Bio Brain cancer Immune infiltration Extracellular matrix Contractility Matrix degradation Microfluidic |
| title | Glioblastoma drives protease-independent extracellular matrix invasion of microglia |
| title_full | Glioblastoma drives protease-independent extracellular matrix invasion of microglia |
| title_fullStr | Glioblastoma drives protease-independent extracellular matrix invasion of microglia |
| title_full_unstemmed | Glioblastoma drives protease-independent extracellular matrix invasion of microglia |
| title_short | Glioblastoma drives protease-independent extracellular matrix invasion of microglia |
| title_sort | glioblastoma drives protease independent extracellular matrix invasion of microglia |
| topic | Brain cancer Immune infiltration Extracellular matrix Contractility Matrix degradation Microfluidic |
| url | http://www.sciencedirect.com/science/article/pii/S259000642500033X |
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