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

Matteo Parri, Laura Pietrovito, Alberto Grandi, Susanna Campagnoli, Elisa De Camilli, Francesca Bianchini, Serena Marchiò, Federico Bussolino, Boquan Jin, Paolo Sarmientos, Guido Grandi, Giuseppe Viale, Piero Pileri, Paola Chiarugi, Renata Grifantini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)881-896
Number of pages16
JournalAngiogenesis
Volume17
Issue number4
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Angiogenesis
  • Angiopoietin-like
  • ANGPTL7
  • Cancer
  • Tissue microarray

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Clinical Biochemistry
  • Medicine(all)

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  • Cite this

    Parri, M., Pietrovito, L., Grandi, A., Campagnoli, S., De Camilli, E., Bianchini, F., Marchiò, S., Bussolino, F., Jin, B., Sarmientos, P., Grandi, G., Viale, G., Pileri, P., Chiarugi, P., & Grifantini, R. (2014). Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer. Angiogenesis, 17(4), 881-896. https://doi.org/10.1007/s10456-014-9435-4