Dataset Information

Secretome analysis of Cx43 expressing cells

ABSTRACT: Extracellular matrix remodeling, degradation and glioma cell motility are critical aspects of glioblastoma multiforme (GBM). Despite being a rich source of potential biomarkers and targets for therapeutic advance, the dynamic changes within the extracellular environment that are specific to GBM cell motility have yet to be fully resolved. The gap junction protein connexin43 (Cx43) increases glioma migration and invasion in a variety of in vitro and in vivo models. In this study, the conditioned media of Cx43-expressing C6 rat glioma cells was found to increase the motility of the parental line. Demonstrating the selective engagement of ECM-remodelling pathways, secretome analysis revealed the near-binary expression of osteopontin and matrix metalloproteinase-3 (MMP3).

INSTRUMENT(S): LTQ Orbitrap, 6530B Q-TOF LC/MS

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

DISEASE(S): Brain Cancer

SUBMITTER: Vincent Chen

LAB HEAD: Vincent Chen

PROVIDER: PXD012175 | Pride | 2019-04-17

REPOSITORIES: Pride

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Publications

Cx43-Associated Secretome and Interactome Reveal Synergistic Mechanisms for Glioma Migration and MMP3 Activation.

Aftab Qurratulain Q Mesnil Marc M Ojefua Emmanuel E Poole Alisha A Noordenbos Jenna J Strale Pierre-Olivier PO Sitko Chris C Le Caitlin C Stoynov Nikolay N Foster Leonard J LJ Sin Wun-Chey WC Naus Christian C CC Chen Vincent C VC

Frontiers in neuroscience 20190319

Extracellular matrix (ECM) remodeling, degradation and glioma cell motility are critical aspects of glioblastoma multiforme (GBM). Despite being a rich source of potential biomarkers and targets for therapeutic advance, the dynamic changes occurring within the extracellular environment that are specific to GBM motility have yet to be fully resolved. The gap junction protein connexin43 (Cx43) increases glioma migration and invasion in a variety of <i>in vitro</i> and <i>in vivo</i> models. In thi ...[more]

PMID: 30941001

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Project description:In this study, we explored the transcriptomic consequences of strong activation of the Notch pathway in embryonic human neural stem cells and in gliomas. For this we used a forced expression of the Notch intracellular domain (NICD). Glioblastoma multiforms (GBMs) are highly vascularized brain tumors containing a subpopulation of multipotent cancer stem cells. These cells closely interact with endothelial cells in neurovascular niches. In this study we have uncovered a close link between the Notch1 pathway and the tumoral vascularization process of GBM stem cells. We observed that although the Notch1 receptor was activated, the typical target proteins (HES5, HEY1, HEY2) were not or barely expressed in two explored GBM stem cell cultures. Notch1 signalling activation by expression of the intracellular form (NICD) in these cells was found to reduce their growth rate and migration which was accompanied by the sharp reduction of neural stem cell transcription factor expression (ASCL1, OLIG2, SOX2) while HEY1/2, KLF9, SNAI2 transcription factors were upregulated. Expression of OLIG2 and growth were restored after termination of Notch1 stimulation. Remarkably, NICD expression induced the expression of pericyte cell markers (NG2, PDGFRb and a-smooth muscle actin (aSMA)) in GBM stem cells. This was paralleled with the induction of several angiogenesis-related factors most notably cytokines (HB-EGF, IL8, PLGF), metalloprotease (MMP9) and adhesion proteins (VCAM-1, ICAM-1, ITGA9). In xenotransplantation experiments, contrasting with the infiltrative and poorly-vascularized tumors obtained with control GBM stem cells, Notch1 stimulation resulted in poorly-disseminating but highly-vascularized grafts containing large vessels with lumen. Notch1-stimulated GBM cells expressed pericyte cell markers and closely associated with endothelial cells. These results reveal an important role for the Notch1 pathway in regulating GBM stem cell plasticity and angiogenic properties. Embryonic human neural progenitors obtained from Lonza, the U87 glioma cell line, and glioma cancer stem cells (Gb4 and Gb7) characterized in Guichet et al. (Glia, 2013, 61(2), 225-39) were infected with lentiviruses expressing YFP or YFP-IRES-NICD (activated form of Notch receptor). After 48h, RNA were extracted for Affymetrix microarray analysis.

Dataset Information

Secretome analysis of Cx43 expressing cells

Publications

Cx43-Associated Secretome and Interactome Reveal Synergistic Mechanisms for Glioma Migration and MMP3 Activation.

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