title: Vascular Endothelial Growth Factor A Regulates the Secretion of Different Angiogenic Factors in Lung Cancer Cells.
abstract: Vascular endothelial growth factor A (VEGFA) is one of the main mediators of angiogenesis in non-small cell lung cancer (NSCLC). Recently, it has been described an autocrine feed-forward loop in NSCLC cells in which tumor-derived VEGFA promoted the secretion of VEGFA itself, amplifying the proangiogenic signal. In order to investigate the role of VEGFA in lung cancer progression, we assessed the effects of recombinant VEGFA on proliferation, migration, and secretion of other angiogenic factors in A549, H1975, and HCC827 NSCLC cell lines. We found that VEGFA did not affect NSCLC cell proliferation and migration. On the other hand, we demonstrated that VEGFA not only produced a strong and persistent increase of VEGFA itself but also significantly induced the secretion of a variety of angiogenic factors, including follistatin (FST), hepatocyte growth factor (HGF), angiopoietin-2 (ANGPT2), granulocyte-colony stimulating factor (G-CSF), interleukin (IL)-8, leptin (LEP), platelet/endothelial cell adhesion molecule 1 (PECAM-1), and platelet-derived growth factor bb (PDGF-BB). PI3K/AKT, RAS/ERK, and STAT3 signalling pathways were found to mediate the effects of VEGFA in NSCLC cell lines. We also observed that VEGFA regulation mainly occurred at post-transcriptional level and that NSCLC cells expressed different isoforms of VEGFA. Collectively, our data suggested that VEGFA contributes to lung cancer progression by inducing a network of angiogenic factors, which might offer potential for therapeutic intervention.
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Frezzetti
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Gallo
authors.affiliation: Laboratory of Pharmacogenomics, Centro di Ricerche Oncologiche di Mercogliano (CROM)-Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Cristin
authors.initials: C
authors.lastname: Roma
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: D'Alessio
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Monica R
authors.initials: MR
authors.lastname: Maiello
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bevilacqua
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: De Luca
mesh_terms: D042501:Angiogenic Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000235:genetics*
chemical_list: D042501:Angiogenic Proteins; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A