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Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer

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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.

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Acknowledgments

The study was funded by Regione Toscana and European grants.

Author information

Authors and Affiliations

  1. Externautics SpA, Via Fiorentina 1, 53100, Siena, Italy

    Matteo Parri, Alberto Grandi, Susanna Campagnoli, Paolo Sarmientos, Piero Pileri & Renata Grifantini

  2. Department of Experimental and Clinical Biomedical Sciences Biochemistry, Human Health Medical School, University of Florence, Viale Morgagni 50, 50134, Florence, Italy

    Laura Pietrovito & Paola Chiarugi

  3. Division of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy

    Elisa De Camilli & Giuseppe Viale

  4. Section of Experimental Pathology and Oncology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy

    Francesca Bianchini

  5. Department of Oncology, University of Turin, Candiolo, Italy

    Serena Marchiò & Federico Bussolino

  6. Lab of Tumor Microenvironment, Candiolo Cancer Institute-IRCCS, Candiolo, Italy

    Serena Marchiò

  7. Lab of Vascular Oncology, Candiolo Cancer Istitute-IRCCS, Candiolo, Italy

    Federico Bussolino

  8. Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi’an, 710032, China

    Boquan Jin

  9. Novartis Vaccines, Siena, Italy

    Guido Grandi

  10. University of Milan, Milan, Italy

    Giuseppe Viale

Authors
  1. Matteo Parri
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  2. Laura Pietrovito
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  3. Alberto Grandi
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  5. Elisa De Camilli
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  10. Paolo Sarmientos
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Corresponding author

Correspondence to Renata Grifantini.

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Matteo Parri and Laura Pietrovito have contributed equally to this work.

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10456_2014_9435_MOESM1_ESM.tif

Supplementary material Fig. 1S. ANGPTL7 quantification in the conditioned medium of ANGPTL7 transfected cells. Western blot analysis of A375 and Ovcar8 cells transfected with the ANGPTL7 coding plasmid or with the empty plasmid (mock). Total cell extract and CM were separated on PAGE-SDS and membranes were probed with an-ANGPTL7 polyclonal antibody (pAb). B) ANGPTL7 quantification in CM. Left panel: quantification by ProSeek assay (OLINK). Different volumes of CM from ANGPTL7 (circle) and mock-transfected (square) Ovcar8 cells were analyzed using an anti-ANGPTL7 pAb versus a standard curve of recombinant ANGPTL7 protein (diamonds), under recommended manufacturer’s conditions. Right panel: Quantification by comparative Western blot. Different volumes of ANGPTL7 CM of Ovcar8 cells were loaded in parallel with different amount of recombinant ANGPTL7 and subjected to Western blot. ANGPTL7 was quantified by densitometric analysis. In both assays ANGPTL7 concentration in ANGPTL7 CM was approx. 0.5 ng/ml. Similar concentrations were found in the CM of HCT15 and A375 transfected cells (TIFF 567 kb)

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Parri, M., Pietrovito, L., Grandi, A. et al. Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer. Angiogenesis 17, 881–896 (2014). https://doi.org/10.1007/s10456-014-9435-4

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  • DOI: https://doi.org/10.1007/s10456-014-9435-4

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