The Junctional Adhesion Molecule C (JAMC) determines the invasive properties of Glioblastoma Stem-like Cells at the endothelial interface

ABSTRACT: The persistence of Glioblastoma Stem-like Cells (GSCs) may account for the high lethality of glioblastoma patients. The GSC reservoir typically resides close to blood vessels, where these cells receive maintenance signals. Upon unfavorable conditions, GSCs escape these niches and spread by exploiting the pre-existing brain vasculature. In both scenarios, GSCs interact with the vascular interface, including the endothelial cells and their matrix. How cell adhesion encountered in their microenvironment serves GSC fate remains ill-defined. By combining ex vivo models, including decellularized matrices, cell co-culture, and organotypic slices, we identified that Junctional Adhesion Molecule C (JAMC) tethers GSCs to endothelial surface. Functionally, JAMC-/- GSCs exhibit an extended spreading on various endothelial-borne supports, with exacerbated invasive, migratory, and mesenchymal-like behaviors, that eventually eroded the survival of GSC tumor-bearing mice. Label-free quantitative proteomics next unveiled that JAMC deletion elicits an up-regulation of integrin expression, concurrent to a down-regulation of the integrin negative regulator, SHARPIN. Data mining of spatial transcriptomics confirmed the association between glioblastoma invasion and the expression pattern of JAMC. While JAMC may provide a retention signal in endothelial niches, the landscape of adhesion molecules anchoring GSCs to vascular surfaces may ultimately coordinate cell migration in defined glioblastoma territories.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Gsc Cell Line

SUBMITTER: Virginie Salnot  

LAB HEAD: Julie Gavard

PROVIDER: PXD062679 | Pride | 2025-08-28

REPOSITORIES: Pride