CD44 expressed by myeloid cells promotes glioma invasion
Glioblastoma multiforme (GBM) is one of the most common and malignant brain tumors in adulthood with a median survival of only 15 months. This poor prognosis is related to GBM’s ability to extensively infiltrate the surrounding brain parenchyma resulting in diffuse spread of neoplastic cells in the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.969787/full |
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| author | Ekaterina L. Ivanova Barbara Costa Tanja Eisemann Sabrina Lohr Pavle Boskovic Pavle Boskovic Viktoria Eichwald Jasmin Meckler Manfred Jugold Veronique Orian-Rousseau Heike Peterziel Heike Peterziel Peter Angel |
| author_facet | Ekaterina L. Ivanova Barbara Costa Tanja Eisemann Sabrina Lohr Pavle Boskovic Pavle Boskovic Viktoria Eichwald Jasmin Meckler Manfred Jugold Veronique Orian-Rousseau Heike Peterziel Heike Peterziel Peter Angel |
| author_sort | Ekaterina L. Ivanova |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is one of the most common and malignant brain tumors in adulthood with a median survival of only 15 months. This poor prognosis is related to GBM’s ability to extensively infiltrate the surrounding brain parenchyma resulting in diffuse spread of neoplastic cells in the brain, responsible for high rate of recurrence. CD44 (Cluster of Differentiation 44) is a transmembrane protein, overexpressed in multiple cancer types, including gliomas, and implicated in cell motility, proliferation and angiogenesis. Multiple studies have investigated the role of CD44 in GBM cells and have highlighted a link between tumor malignancy and CD44 expression. However up to date, little is known of the role of CD44 on cells from the tumor microenvironment (TME). Here, we have investigated a potential role of CD44 in the TME in regards to GBM invasiveness. Using an ex-vivo organotypic brain slice invasion assay, we show that absence of CD44 from the TME impairs the ability of glioma cells to invade the surrounding brain parenchyma. By deleting CD44 in the astrocytic, endothelial and myeloid compartments, we show that it is specifically CD44 expression in myeloid cells that is responsible for the observed phenotype. Combining in vivo studies in cell-specific knock-out mice and in vitro analyses on primary microglia we demonstrate that myeloid CD44 is implicated in Toll Like Receptor 2 signaling and is a major regulator of Matrix metalloproteinase 9 expression. |
| first_indexed | 2024-12-10T17:24:16Z |
| format | Article |
| id | doaj.art-3a278d7ba05a4957a636ec5b29a1a6c1 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T17:24:16Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3a278d7ba05a4957a636ec5b29a1a6c12022-12-22T01:39:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.969787969787CD44 expressed by myeloid cells promotes glioma invasionEkaterina L. Ivanova0Barbara Costa1Tanja Eisemann2Sabrina Lohr3Pavle Boskovic4Pavle Boskovic5Viktoria Eichwald6Jasmin Meckler7Manfred Jugold8Veronique Orian-Rousseau9Heike Peterziel10Heike Peterziel11Peter Angel12Division of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, GermanyCore Facility Small Animal Imaging Center, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyCore Facility Small Animal Imaging Center, German Cancer Research Center (DKFZ), Heidelberg, GermanyKarlsruhe Institute of Technology (KIT), Institute of Biological and Chemical Systems – Functional Molecular Systems (IBCS-FMS), Hermann-von-Helmholtz-Platz 1, Eggenstein-Leopoldshafen, GermanyDivision of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyClinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, GermanyGlioblastoma multiforme (GBM) is one of the most common and malignant brain tumors in adulthood with a median survival of only 15 months. This poor prognosis is related to GBM’s ability to extensively infiltrate the surrounding brain parenchyma resulting in diffuse spread of neoplastic cells in the brain, responsible for high rate of recurrence. CD44 (Cluster of Differentiation 44) is a transmembrane protein, overexpressed in multiple cancer types, including gliomas, and implicated in cell motility, proliferation and angiogenesis. Multiple studies have investigated the role of CD44 in GBM cells and have highlighted a link between tumor malignancy and CD44 expression. However up to date, little is known of the role of CD44 on cells from the tumor microenvironment (TME). Here, we have investigated a potential role of CD44 in the TME in regards to GBM invasiveness. Using an ex-vivo organotypic brain slice invasion assay, we show that absence of CD44 from the TME impairs the ability of glioma cells to invade the surrounding brain parenchyma. By deleting CD44 in the astrocytic, endothelial and myeloid compartments, we show that it is specifically CD44 expression in myeloid cells that is responsible for the observed phenotype. Combining in vivo studies in cell-specific knock-out mice and in vitro analyses on primary microglia we demonstrate that myeloid CD44 is implicated in Toll Like Receptor 2 signaling and is a major regulator of Matrix metalloproteinase 9 expression.https://www.frontiersin.org/articles/10.3389/fonc.2022.969787/fullglioblastomaCD44tumor microenvironmentmicrogliaTLR2MMP9 |
| spellingShingle | Ekaterina L. Ivanova Barbara Costa Tanja Eisemann Sabrina Lohr Pavle Boskovic Pavle Boskovic Viktoria Eichwald Jasmin Meckler Manfred Jugold Veronique Orian-Rousseau Heike Peterziel Heike Peterziel Peter Angel CD44 expressed by myeloid cells promotes glioma invasion Frontiers in Oncology glioblastoma CD44 tumor microenvironment microglia TLR2 MMP9 |
| title | CD44 expressed by myeloid cells promotes glioma invasion |
| title_full | CD44 expressed by myeloid cells promotes glioma invasion |
| title_fullStr | CD44 expressed by myeloid cells promotes glioma invasion |
| title_full_unstemmed | CD44 expressed by myeloid cells promotes glioma invasion |
| title_short | CD44 expressed by myeloid cells promotes glioma invasion |
| title_sort | cd44 expressed by myeloid cells promotes glioma invasion |
| topic | glioblastoma CD44 tumor microenvironment microglia TLR2 MMP9 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.969787/full |
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