Journal Article

DKFZ-2024-01323

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Effects of tumor treating fields (TTFields) on human mesenchymal stromal cells.

Strack, M.DKFZ* ; Kückelhaus, J. ; Diebold, M. ; Wuchter, P. ; Huber, P. E. ; Schnell, O. ; Sankowski, R. ; Prinz, M. ; Grosu, A.-L.DKFZ* ; Heiland, D. H. ; Nicolay, N. H.DKFZ* ; Rühle, A. (Last author)DKFZ*

2024
Springer Science + Business Media B.V Dordrecht [u.a.]

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Please use a persistent id in citations: doi:10.1007/s11060-024-04740-0

Abstract: Mesenchymal stromal cells (MSCs) within the glioblastoma microenvironment have been shown to promote tumor progression. Tumor Treating Fields (TTFields) are alternating electric fields with low intensity and intermediate frequency that exhibit anti-tumorigenic effects. While the effects of TTFields on glioblastoma cells have been studied previously, nothing is known about the influence of TTFields on MSCs.Single-cell RNA sequencing and immunofluorescence staining were employed to identify glioblastoma-associated MSCs in patient samples. Proliferation and clonogenic survival of human bone marrow-derived MSCs were assessed after TTFields in vitro. MSC' characteristic surface marker expression was determined using flow cytometry, while multi-lineage differentiation potential was examined with immunohistochemistry. Apoptosis was quantified based on caspase-3 and annexin-V/7-AAD levels in flow cytometry, and senescence was assessed with ß-galactosidase staining. MSCs' migratory potential was evaluated with Boyden chamber assays.Single-cell RNA sequencing and immunofluorescence showed the presence of glioblastoma-associated MSCs in patient samples. TTFields significantly reduced proliferation and clonogenic survival of human bone marrow-derived MSCs by up to 60% and 90%, respectively. While the characteristic surface marker expression and differentiation capacity were intact after TTFields, treatment resulted in increased apoptosis and senescence. Furthermore, TTFields significantly reduced MSCs' migratory capacity.We could demonstrate the presence of tumor-associated MSCs in glioblastoma patients, providing a rationale to study the impact of TTFields on MSCs. TTFields considerably increase apoptosis and senescence in MSCs, resulting in impaired survival and migration. The results provide a basis for further analyses on the role of MSCs in glioblastoma patients receiving TTFields.

Keyword(s): Glioma ; Mesenchymal stem cells ; Mesenchymal stromal cells ; Tumor microenvironment

Note: #LA:E055# / 2024 Sep;169(2):329-340

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)
2. E055 KKE Molekulare Radioonkologie (E055)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2024

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; DEAL Springer ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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