The ablation of the matricellular protein EMILIN2 causes defective vascularization due to impaired EGFR-dependent IL-8 production affecting tumor growth

Oncogene
Alice PaulittiMaurizio Mongiat

Abstract

EMILIN2 is an extracellular matrix constituent playing an important role in angiogenesis; however, the underlying mechanism is unknown. Here we show that EMILIN2 promotes angiogenesis by directly binding epidermal growth factor receptor (EGFR), which enhances interleukin-8 (IL-8) production. In turn, IL-8 stimulates the proliferation and migration of vascular endothelial cells. Emilin2 null mice were generated and exhibited delayed retinal vascular development, which was rescued by the administration of the IL-8 murine ortholog MIP-2. Next, we assessed tumor growth and tumor-associated angiogenesis in these mice. Tumor cell growth in Emilin2 null mice was impaired as well as the expression of MIP-2. The vascular density of the tumors developed in Emilin2 null mice was prejudiced and vessels perfusion, as well as response to chemotherapy, decreased. Accordingly, human tumors expressing high levels of EMILIN2 were more responsive to chemotherapy. These results point at EMILIN2 as a key microenvironmental cue affecting vessel formation and unveil the possibility to develop new prognostic tools to predict chemotherapy efficacy.

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Citations

Dec 12, 2018·Stem Cells Translational Medicine·Franca M R WitjasTon J Rabelink
Mar 25, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Qiuhan HuaYiguo Jiang
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Jul 25, 2021·International Journal of Molecular Sciences·Albina FejzaEva Andreuzzi
Jul 20, 2021·Brain Research Bulletin·Li-Chong WangXiao-Li Shen

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Methods Mentioned

BETA
protein array
enzyme-linked
PCR
ELISA
immunoprecipitation
pull-down
surface plasmon resonance
Electrophoresis
PCRs
transfection

Software Mentioned

NextBio tool
SigmaPlotGraphPad Prism
LEICA Time - lapse System
NextBio
CellQuest

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