TY - JOUR
T1 - Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer
AU - Parri, Matteo
AU - Pietrovito, Laura
AU - Grandi, Alberto
AU - Campagnoli, Susanna
AU - De Camilli, Elisa
AU - Bianchini, Francesca
AU - Marchiò, Serena
AU - Bussolino, Federico
AU - Jin, Boquan
AU - Sarmientos, Paolo
AU - Grandi, Guido
AU - Viale, Giuseppe
AU - Pileri, Piero
AU - Chiarugi, Paola
AU - Grifantini, Renata
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Angiopoietin-like (ANGPTL) proteins are secreted proteins showing structural similarity to members of the angiopoietin family. Some ANGPTL proteins possess pleiotropic activities, being involved in cancer lipid, glucose energy metabolisms, and angiogenesis. ANGPTL7 is the less characterized member of the family whose functional role is only marginally known. In this study, we provide experimental evidences that ANGPTL7 is over-expressed in different human cancers. To understand the role played by ANGPTL7 in tumor biology, we asked whether ANGPTL7 is endogenously expressed by malignant cells or in response to environmental stimuli. We found that ANGPTL7 is marginally expressed under standard growth condition while it is specifically up-regulated by hypoxia. Interestingly, the protein is secreted and partially associated with the exosomal fraction, suggesting that it could be found in the systemic circulation of oncologic patients and act in an endocrine way. Moreover, we found that ANGPTL7 exerts a pro-angiogenetic effect on human differentiated endothelial cells by stimulating their proliferation, motility, invasiveness, and capability to form capillary-like networks while it does not stimulate progenitor endothelial cells. Finally, we showed that ANGPTL7 promotes vascularization in vivo in the mouse Matrigel sponge assay, thereby accrediting this molecule as a pro-angiogenic factor.
AB - Angiopoietin-like (ANGPTL) proteins are secreted proteins showing structural similarity to members of the angiopoietin family. Some ANGPTL proteins possess pleiotropic activities, being involved in cancer lipid, glucose energy metabolisms, and angiogenesis. ANGPTL7 is the less characterized member of the family whose functional role is only marginally known. In this study, we provide experimental evidences that ANGPTL7 is over-expressed in different human cancers. To understand the role played by ANGPTL7 in tumor biology, we asked whether ANGPTL7 is endogenously expressed by malignant cells or in response to environmental stimuli. We found that ANGPTL7 is marginally expressed under standard growth condition while it is specifically up-regulated by hypoxia. Interestingly, the protein is secreted and partially associated with the exosomal fraction, suggesting that it could be found in the systemic circulation of oncologic patients and act in an endocrine way. Moreover, we found that ANGPTL7 exerts a pro-angiogenetic effect on human differentiated endothelial cells by stimulating their proliferation, motility, invasiveness, and capability to form capillary-like networks while it does not stimulate progenitor endothelial cells. Finally, we showed that ANGPTL7 promotes vascularization in vivo in the mouse Matrigel sponge assay, thereby accrediting this molecule as a pro-angiogenic factor.
KW - Angiogenesis
KW - Angiopoietin-like
KW - ANGPTL7
KW - Cancer
KW - Tissue microarray
UR - http://www.scopus.com/inward/record.url?scp=84907592713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907592713&partnerID=8YFLogxK
U2 - 10.1007/s10456-014-9435-4
DO - 10.1007/s10456-014-9435-4
M3 - Article
C2 - 24903490
AN - SCOPUS:84907592713
VL - 17
SP - 881
EP - 896
JO - Angiogenesis
JF - Angiogenesis
SN - 0969-6970
IS - 4
ER -