Exosomes derived from 5-fluorouracil-resistant colon cancer cells are enriched in GDF15 and can promote angiogenesis

Journal of Cancer
Xixi ZhengBangwei Cao

Abstract

Background: Angiogenesis is important for tumor proliferation and distant metastasis. However, the role of drug-resistant tumor cells in angiogenesis remains largely unknown. Current anti-angiogenic strategies also have limitations and it would be useful to develop novel targets and treatment strategies. Methods: Differential ultracentrifugation was used to isolate conditioned medium-derived exosomes from 5-flurouracil (5-FU)-sensitive or -resistant colon cancer cells. Exosome endocytosis into human umbilical vein endothelial cells was observed via immunofluorescence. Differentially expressed proteins in the exosomes were confirmed via qRT-PCR and Western blotting. The angiogenic capacity of endothelial cells was evaluated using cell function assays and a rat model of abdominal aortic neovascularization. The underlying mechanisms were verified using qRT-PCR and Western blotting assays. Immunohistochemistry was used to evaluate in vivo angiogenesis. Results: We observed that the conditioned medium and exosomes from 5-FU-resistant colon cancer cells could promote angiogenesis. Exosomal growth/differentiation factor 15 (GDF15) was a potent inducer of this angiogenesis in vitro by inhibiting the Smad signaling pathway, thus increas...Continue Reading

Citations

Aug 8, 2021·International Journal of Molecular Sciences·Bohan ChenLei Zhang

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
transmission electron microscopy
phase contrast microscopy
confocal microscopy
PCR
immunoprecipitation
protein assay

Software Mentioned

ImageJ
GraphPad Prism

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