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EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF.

Khayati F, Pérez-Cano L, Maouche K, Sadoux A, Boutalbi Z, Podgorniak MP, Maskos U, Setterblad N, Janin A, Calvo F, Lebbé C, Menashi S, Fernandez-Recio J, Mourah S - Oncotarget (2015)

Bottom Line: EMMPRIN/CD147 is mainly known for its protease inducing function but a role in promoting tumor angiogenesis has also been demonstrated.This study provides evidence that EMMPRIN is a new coreceptor for the VEGFR-2 tyrosine kinase receptor in both endothelial and tumor cells, as it directly interacts with it and regulates its activation by its VEGF ligand, signalling and functional consequences both in vitro and in vivo.EMMPRIN is overexpressed in cancer and hence is able to further potentiate VEGFR-2 activation, suggesting that a combinatory therapy of an antiangiogenic drug together with an inhibitor of EMMPRIN/VEGFR-2 interaction may have a greater impact on inhibiting angiogenesis and malignancy.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.

ABSTRACT
EMMPRIN/CD147 is mainly known for its protease inducing function but a role in promoting tumor angiogenesis has also been demonstrated. This study provides evidence that EMMPRIN is a new coreceptor for the VEGFR-2 tyrosine kinase receptor in both endothelial and tumor cells, as it directly interacts with it and regulates its activation by its VEGF ligand, signalling and functional consequences both in vitro and in vivo. Computational docking analyses and mutagenesis studies identified a molecular binding site in the extracellular domain of EMMPRIN located close to the cell membrane and containing the amino acids 195/199. EMMPRIN is overexpressed in cancer and hence is able to further potentiate VEGFR-2 activation, suggesting that a combinatory therapy of an antiangiogenic drug together with an inhibitor of EMMPRIN/VEGFR-2 interaction may have a greater impact on inhibiting angiogenesis and malignancy.

No MeSH data available.


Related in: MedlinePlus

EMMPRIN silencing decreases EMMPRIN/VEGFR-2 interaction in endothelial and tumor cellsCells were transfected with EMMPRIN siRNA or scrambled siRNA prior to in situ PLA for EMMPRIN-VEGFR-2 interaction. Cell nuclei were stained with DAPI (blue), magnification x 63. The detected dimers (EMMPRIN/VEGFR-2) are represented as red dots. Representative images of three independent experiments are shown. Quantification of PLA signals was performed on ~150 transfected cells per condition in three independent experiments; mean PLA signal/cell ± SD are plotted. ***P ≤ 0.0001.
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Figure 2: EMMPRIN silencing decreases EMMPRIN/VEGFR-2 interaction in endothelial and tumor cellsCells were transfected with EMMPRIN siRNA or scrambled siRNA prior to in situ PLA for EMMPRIN-VEGFR-2 interaction. Cell nuclei were stained with DAPI (blue), magnification x 63. The detected dimers (EMMPRIN/VEGFR-2) are represented as red dots. Representative images of three independent experiments are shown. Quantification of PLA signals was performed on ~150 transfected cells per condition in three independent experiments; mean PLA signal/cell ± SD are plotted. ***P ≤ 0.0001.

Mentions: The specificity of EMMPRIN/VEGFR-2 interaction was demonstrated by the decrease in the immunoprecipitated (IP) complex when EMMPRIN expression was silenced using siRNA strategy (Figure 1D). This was confirmed by PLA assay showing a large decrease in the number of red dots of cells transfected with EMMPRIN siRNA in both endothelial and tumor cells compared with its corresponding scrambled siRNA (Figure 2). Similar results were obtained with BLM melanoma cells (not shown).


EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF.

Khayati F, Pérez-Cano L, Maouche K, Sadoux A, Boutalbi Z, Podgorniak MP, Maskos U, Setterblad N, Janin A, Calvo F, Lebbé C, Menashi S, Fernandez-Recio J, Mourah S - Oncotarget (2015)

EMMPRIN silencing decreases EMMPRIN/VEGFR-2 interaction in endothelial and tumor cellsCells were transfected with EMMPRIN siRNA or scrambled siRNA prior to in situ PLA for EMMPRIN-VEGFR-2 interaction. Cell nuclei were stained with DAPI (blue), magnification x 63. The detected dimers (EMMPRIN/VEGFR-2) are represented as red dots. Representative images of three independent experiments are shown. Quantification of PLA signals was performed on ~150 transfected cells per condition in three independent experiments; mean PLA signal/cell ± SD are plotted. ***P ≤ 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496396&req=5

Figure 2: EMMPRIN silencing decreases EMMPRIN/VEGFR-2 interaction in endothelial and tumor cellsCells were transfected with EMMPRIN siRNA or scrambled siRNA prior to in situ PLA for EMMPRIN-VEGFR-2 interaction. Cell nuclei were stained with DAPI (blue), magnification x 63. The detected dimers (EMMPRIN/VEGFR-2) are represented as red dots. Representative images of three independent experiments are shown. Quantification of PLA signals was performed on ~150 transfected cells per condition in three independent experiments; mean PLA signal/cell ± SD are plotted. ***P ≤ 0.0001.
Mentions: The specificity of EMMPRIN/VEGFR-2 interaction was demonstrated by the decrease in the immunoprecipitated (IP) complex when EMMPRIN expression was silenced using siRNA strategy (Figure 1D). This was confirmed by PLA assay showing a large decrease in the number of red dots of cells transfected with EMMPRIN siRNA in both endothelial and tumor cells compared with its corresponding scrambled siRNA (Figure 2). Similar results were obtained with BLM melanoma cells (not shown).

Bottom Line: EMMPRIN/CD147 is mainly known for its protease inducing function but a role in promoting tumor angiogenesis has also been demonstrated.This study provides evidence that EMMPRIN is a new coreceptor for the VEGFR-2 tyrosine kinase receptor in both endothelial and tumor cells, as it directly interacts with it and regulates its activation by its VEGF ligand, signalling and functional consequences both in vitro and in vivo.EMMPRIN is overexpressed in cancer and hence is able to further potentiate VEGFR-2 activation, suggesting that a combinatory therapy of an antiangiogenic drug together with an inhibitor of EMMPRIN/VEGFR-2 interaction may have a greater impact on inhibiting angiogenesis and malignancy.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.

ABSTRACT
EMMPRIN/CD147 is mainly known for its protease inducing function but a role in promoting tumor angiogenesis has also been demonstrated. This study provides evidence that EMMPRIN is a new coreceptor for the VEGFR-2 tyrosine kinase receptor in both endothelial and tumor cells, as it directly interacts with it and regulates its activation by its VEGF ligand, signalling and functional consequences both in vitro and in vivo. Computational docking analyses and mutagenesis studies identified a molecular binding site in the extracellular domain of EMMPRIN located close to the cell membrane and containing the amino acids 195/199. EMMPRIN is overexpressed in cancer and hence is able to further potentiate VEGFR-2 activation, suggesting that a combinatory therapy of an antiangiogenic drug together with an inhibitor of EMMPRIN/VEGFR-2 interaction may have a greater impact on inhibiting angiogenesis and malignancy.

No MeSH data available.


Related in: MedlinePlus