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.

Cd11b+ myeloid cells support hepatic metastasis through down‐regulation of angiopoietin‐like 7 in cancer cells

“…Moreover, removal of ANGPTL7 with antibody restored endothelial cell proliferation, migration, and tube formation to control levels. These experiments differ from those of Parri et al, who found that recombinant ANGPTL7 augmented endothelial proliferation and migration . In our hands the same bacteria‐derived recombinant protein had no effect on the endothelial cells in any of the assays we used (http://onlinelibrary.wiley.com/doi/10.1002/hep.27838/suppinfo).…”

“…We found ANGPTL7 to be antiangiogenic. In general, attribution of angiogenic activities to ANGPTL7 has been inconsistent, with some studies reporting proangiogenic effects and others suggesting antiangiogenic functions . These discrepancies may be attributed to differences in assay conditions, cell types used, and species‐specific signaling.…”

Identification, by systematic RNA sequencing, of novel candidate biomarkers and therapeutic targets in human soft tissue tumors

“…28 Just recently, ANGPTL7 was reported to be a hypoxia-driven proangiogenetic factor upregulated in cancer cells that can induce malignant behavior in human prostate cancer cells: it could be an interesting candidate to profile across many schwannomas, to determine if its expression levels correlate with malignant progression. 29,30 Many of the upregulated genes that we identified in our study have been functionally characterized as part of the inflammatory response, a hallmark enabling characteristic that can support multiple cancer capabilities. 31 MADCAM1, another highly upregulated gene in our angiosarcoma samples, is associated with the onset and progression of multiple gastric inflammatory diseases and is also upregulated in melanoma cells.…”

Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells

“…After 12 h incubation on Matrigel at 37 °C, the plates were photographed under a phase contrast microscope. The degree of tubule formation was quantified by counting the branching points in four randomly chosen fields from each well [51]. …”