Journal Article

DKFZ-2022-01968

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CD44 expressed by myeloid cells promotes glioma invasion.

Ivanova, E. (First author)DKFZ* ; Costa, B.DKFZ* ; Eisemann, T.DKFZ* ; Lohr, S.DKFZ* ; Boskovic, P.DKFZ* ; Eichwald, V.DKFZ* ; Meckler, J.DKFZ* ; Jugold, M.DKFZ* ; Orian-Rousseau, V. ; Peterziel, H.DKFZ* ; Angel, P. (Last author)DKFZ*

2022
Frontiers Media Lausanne

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Please use a persistent id in citations: doi:10.3389/fonc.2022.969787

Abstract: 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.

Keyword(s): CD44 ; MMP9 ; TLR2 ; glioblastoma ; microglia ; tumor microenvironment

Note: DKFZ/ZMBH Alliance /#EA: A100#LA:A100#

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Contributing Institute(s):

1. A100 Signaltransduktion/ Wachstumskontrolle (A100)
2. Core Facility Kleinbildgebung (W240)
3. KKE Pädiatrische Onkologie (B310)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2022

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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