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Article Dans Une Revue STEM CELLS Année : 2012

Differential Proteomic Analysis of Human Glioblastoma and Neural Stem Cells Reveals HDGF as a Novel Angiogenic Secreted Factor

Suzanne Delfortrie
  • Fonction : Auteur
Sébastien Pinte
  • Fonction : Auteur
Virginie Mattot
  • Fonction : Auteur
Chantal Samson
  • Fonction : Auteur
Gaëlle Villain
  • Fonction : Auteur
Bertrand Caetano
  • Fonction : Auteur
Géraldine Lauridant-Philippin
  • Fonction : Auteur
Marie-Christine Baranzelli
  • Fonction : Auteur
Jacques Bonneterre
  • Fonction : Auteur
  • PersonId : 1077661
  • IdRef : 060118776
François Trottein
  • Fonction : Auteur
Christelle Faveeuw
  • Fonction : Auteur

Résumé

Abstract Downregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines [IFN-γ, interleukin-12 (IL-12)] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-γ. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control. Cancer Res; 71(23); 7176–86. ©2011 AACR.

Domaines

Cancer

Dates et versions

hal-04277389 , version 1 (09-11-2023)

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Citer

Suzanne Delfortrie, Sébastien Pinte, Virginie Mattot, Chantal Samson, Gaëlle Villain, et al.. Differential Proteomic Analysis of Human Glioblastoma and Neural Stem Cells Reveals HDGF as a Novel Angiogenic Secreted Factor. STEM CELLS, 2012, 30 (5), pp.845-853. ⟨10.1158/0008-5472.CAN-11-1301⟩. ⟨hal-04277389⟩
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