Publication: Aberrant expression and association of VEGF and Dll4/Notch pathway molecules under hypoxia in patients with lung cancer
Authors
Yu, Shuang ; Sun, Jianhua Sun ; Zhang, Jingru ; Xu, Xingfang ; Li, Hong ; Shan, Baozhong ; Tian, Tian ; Wang, Hongchun ; Ma, Daoxin ; Ji, Chunyan
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Tumor angiogenesis plays important roles in
the pathogenesis and prognosis of lung cancer. Both
vascular endothelial growth factor (VEGF) and
Dll4/Notch pathways are critical for angiogenesis,
whereas their relationship under hypoxia in lung cancer
remains unknown. Thus, in the present study, we
evaluated the expression of VEGF and Dll4/Notch
signaling molecules, and assessed their association with
the microvessel density (CD31) and hypoxia (HIF1a) in
lung cancer and normal lung tissues using immunohistochemical
and Real-time RT-PCR techniques. Then,
we investigated the biological function of Dll4 by
transfecting Dll4 into HUVECs. In lung cancer tissues,
Notch pathway molecules (HES1) and VEGF pathway
molecules (VEGFR1 and VEGFR2) were significantly
up-regulated, while the ratio of VEGFR1/VEGFR2 was
decreased. CD31 and HIF1a were also found to be
elevated in lung cancer. VEGFR1 was negatively
correlated with Notch1 while positively correlated with
Dll4. CD31 was positively correlated with HIF1a but
negatively correlated with VEGFR1. Moreover, HIF1a
was nearly positively correlated with HES1 in lung
cancer tissues. After transfection, Dll4, Notch1 and
VEGFR1 were up-regulated while VEGF and VEGFR2
were down-regulated in Dll4-transfected HUVECs
compared with controls. Also, our findings suggest that
the expression of VEGF and VEGFR2 increased
gradually with the disease progression of lung cancer. In
summary, VEGF and Notch signaling pathway
molecules were overexpressed in lung cancer, which
positively correlates with hypoxia (HIF1a) and
angiogenesis (CD31). There might be a negative
feedback loop between VEGF and Dll4/Notch signaling
pathway in lung tumor angiogenesis.
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