title: Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer.
abstract: 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.
authors.affiliation: Externautics SpA, Via Fiorentina 1, 53100, Siena, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Parri
authors.forename: Laura
authors.initials: L
authors.lastname: Pietrovito
authors.forename: Alberto
authors.initials: A
authors.lastname: Grandi
authors.forename: Susanna
authors.initials: S
authors.lastname: Campagnoli
authors.forename: Elisa
authors.initials: E
authors.lastname: De Camilli
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchini
authors.forename: Serena
authors.initials: S
authors.lastname: Marchiò
authors.forename: Federico
authors.initials: F
authors.lastname: Bussolino
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
authors.forename: Paolo
authors.initials: P
authors.lastname: Sarmientos
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Piero
authors.initials: P
authors.lastname: Pileri
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
authors.forename: Renata
authors.initials: R
authors.lastname: Grifantini
mesh_terms: D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004703:Endocrine System; D042783:Endothelial Cells / Q000166:cytology; D055354:Exosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation
chemical_list: C530622:ANGPTL7 protein, human; D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D017077:Culture Media, Conditioned