Autor: |
Jiale Zhang, Shan Jiang, Xingju Zhang, Ying Wan, Bin Xiao, Fei Li, Ying Tang |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
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DOI: |
10.1101/708826 |
Popis: |
The percentage of MDSC population in peripheral blood is significantly increased in lung cancer patients. The accumulation of MDSC contributes to the development of a tumour-associated immune suppressive environment. But the mechanism mediating MDSC accumulation in lung cancer patients is elusive. We found that exosomes from Lewis lung cancer cells (LLC-Exo) can be taken up by the mice bone marrow cells and then promote MDSC expansion, which enhance tumour growth. Mechanistically, during the induction of MDSC from the bone marrow cells, miR-21a from LLC-Exo can stimulate BM cells to produce more IL-6 by inhibitingpdcd4expression post-transcriptionally. Autocrine IL-6 induces tyrosine 705(Y705) of STAT3 to be phosphorylated during MDSC expansion. LLC-Exo with miR-21a deletion lost its ability to stimulate IL-6 production, STAT3 activation and MDSC expansion. These results demonstrate that lung cancer cell-derived exosomes promote functional MDSC expansion through activation of miR-21a/PDCD4/IL-6/STAT3 pathway. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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