Metformin inhibits esophageal squamous cell carcinoma-induced angiogenesis by suppressing JAK/STAT3 signaling pathway

Oncotarget
Yi YangZi-ming Dong

Abstract

Although it has been known that the tumor microenvironment affects angiogenesis, the precise mechanism remains unclear. In this study, we simulated the microenvironment of human esophageal squamous cell carcinoma (ESCC) by tumor conditioned medium (TCM) to assess the influence on normal endothelial cells (NECs). We found that the TCM-induced NECs showed enhanced angiogenic properties, such as migration, invasion and tube formation. Moreover, the TCM-induced NECs expressed tumor endothelial cells (TECs) markers at higher levels, which indicated that TCM probably promoted tumor angiogenesis by coercing NECs to change toward TECs. The microarray gene expression analysis indicated that TCM induced great changes in the genome of NECs and altered many regulatory networks, especially c-MYC and JAK/STAT3 signaling pathway. More importantly, we investigated the anti-angiogenic effect of metformin, and found that metformin abrogated the ESCC microenvironment-induced transition of NECs toward TECs by inhibiting JAK/STAT3/c-MYC signaling pathway. Furthermore, we verified the anti-angiogenic activity of metformin in vivo by a human ESCC patient-derived xenograft (PDX) mouse model for the first time. Taken together, our research provides a n...Continue Reading

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Citations

May 29, 2019·The Cancer Journal·Kira L RussellMichael T Lotze
May 29, 2020·Human Vaccines & Immunotherapeutics·Jun ZhaoJing Lu
Jan 11, 2019·Frontiers in Oncology·Fabiana Henriques Machado de MeloWagner Ricardo Montor
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Mar 22, 2021·Cancer Chemotherapy and Pharmacology·Mohammad Rafi KhezriMorteza Ghasemnejad-Berenji
Jul 27, 2021·Current Opinion in Pharmacology·Antonio J León-GonzálezRaúl M Luque

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Methods Mentioned

BETA
xenograft
PCR
protein assay
chips
ELISA

Software Mentioned

Molecule
Significance Analysis of Microarrays Software ( SAM
KYGG
BioCarta
GenMAPP
image J
Affymetrix GeneChip Operating Software GCOS
GraphPad
GraphPad PRISM

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