Sengupta, S and Mondal, M and Prasasvi, KR and Mukherjee, A and Magod, P and Urbach, S and Friedmann-Morvinski, D and Marin, P and Somasundaram, K (2022) Differentiated glioma cell-derived fibromodulin activates integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth. In: eLife, 11 .
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Abstract
Cancer stem cells (CSCs) alone can initiate and maintain tumors, but the function of non-cancer stem cells (non-CSCs) that form the tumor bulk remains poorly understood. Proteomic analysis showed a higher abundance of the extracellular matrix small leucine-rich proteoglycan fibro-modulin (FMOD) in the conditioned medium of differentiated glioma cells (DGCs), the equivalent of glioma non-CSCs, compared to that of glioma stem-like cells (GSCs). DGCs silenced for FMOD fail to cooperate with co-implanted GSCs to promote tumor growth. FMOD downregulation neither affects GSC growth and differentiation nor DGC growth and reprogramming in vitro. DGC-secreted FMOD promotes angiogenesis by activating integrin-dependent Notch signaling in endothelial cells. Furthermore, conditional silencing of FMOD in newly generated DGCs in vivo inhibits the growth of GSC-initiated tumors due to poorly developed vasculature and increases mouse survival. Collec-tively, these findings demonstrate that DGC-secreted FMOD promotes glioma tumor angiogenesis and growth through paracrine signaling in endothelial cells and identifies a DGC-produced protein as a potential therapeutic target in glioma.
| Item Type: | Journal Article |
|---|---|
| Publication: | eLife |
| Publisher: | eLife Sciences Publications Ltd |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 28 Jul 2022 05:17 |
| Last Modified: | 28 Jul 2022 05:17 |
| URI: | https://eprints.iisc.ac.in/id/eprint/75008 |
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