Basic & Clinical Medicine ›› 2015, Vol. 35 ›› Issue (8): 1072-1077.

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Effects of exosomes derived from breast cancer cell on tumor angiogenesis and its mechanism

  

  • Received:2014-09-25 Revised:2015-03-30 Online:2015-08-05 Published:2015-07-15

Abstract: Objective To study the effects of breast cancer cell exosomes on HUVECs,and to explore the possible mechanism. Methods Exosomes were prepared from the supernatants of MDA-MB-231 cells by density gradient ultracentrifugation. HUVECs proliferation after treated with Exosomes was measured by MTT. FACS was used to detect the distribution of HUVECs cell cycle. Transwell was used to HUVECs migration. Matrigel glue was used to detectd changes in tube formation.PCR was used to detect the expression of EGFR and VEGF mRNA.ELISA and Western blot was used to detect EGFR and the expression of its downstream protein,such as ERK & Akt, and VEGF / VEGFR2.Results Exosomes promoted HUVECs proliferation in a time-and dose-dependent manner(P<0.05),and HUVECs in S-phase G1-phase and the rate of G1/S phase of the cell cycle (P<0.05). The migration and capability of tube formation of HUVECs were enhanced by Exosomes(P<0.05).And Exosomes promoted the expression of EGFR, phospho-ERK & Akt protein, the secretion of VEGF protein increased, and the VEGF / VEGFR2 protein in HUVECs increased.Conclusion Breast cancer cell Exosomes promote HUVECs proliferation,migration and the capability of tube formation, possibly via the expression of EGFR and activating the MAPK/ERK,PI3K/Akt and VEGF/VEGFR2.

Key words: Exosomes, Breast cancer, Tumor angiogenesis

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