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Vascular Endothelial Growth Factor A Regulates the Secretion of Different Angiogenic Factors in Lung Cancer Cells
Author(s) -
Frezzetti Daniela,
Gallo Marianna,
Roma Cristin,
D'Alessio Amelia,
Maiello Monica R.,
Bevilacqua Simona,
Normanno Nicola,
De Luca Antonella
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25243
Subject(s) - vascular endothelial growth factor a , angiogenesis , cancer research , autocrine signalling , vascular endothelial growth factor , biology , growth factor , vascular endothelial growth factor c , cell culture , receptor , biochemistry , genetics , vegf receptors
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. J. Cell. Physiol. 231: 1514–1521, 2016. © 2015 Wiley Periodicals, Inc.