Abstract

BackgroundPrevious studies have reported that soluble fms‐like tyrosine kinase‐1 (sFlt‐1) possesses anti‐tumor effects by inhibiting angiogenesis in many cancers. Exosomes can be engineered as delivery vehicles for transferring functional biomolecules, such as proteins, lipids, and nucleic acids (DNA, mRNA, and miRNA) to target cells to affect inflammation, apoptosis, and angiogenesis. The purpose of this study was to investigate whether exosomes can function as efficient carriers of sFlt‐1 in vitro and in vivo, to play a role in SCLC therapy.MethodsWe adopted three different methods: TEM, NTA and western blot analysis to characterize the cell‐derived exosomes from NCI‐H69 SCLC cell line and normal bronchial epithelial BEAS‐2B cell line. we next explored the effects of these exosomes on HUVE cell proliferation and migration in vitro.To verify sFlt‐1‐loaded exosomes suppress the tumor growth in vivo,we established subcutaneous xenografts in nude mice using the NCI‐H69 cell line.ResultsWe observed that NCI‐H69‐exo significantly increased human umbilical vein endothelial cells (HUVEC) migration compared to BEAS‐2B‐exo in vitro and in vivo. sFlt‐1 protein expression was statistically higher in BEAS‐2B‐exo than NCI‐H69‐exo. sFlt‐1 protein or sFlt‐1‐enriched exosomes can inhibit the migration of HUVECs. Furthermore, sFlt‐1‐enriched exosomes exhibited higher inhibition efficacy on pro‐angiogenesis of NCI‐H69‐exo in comparison with the same concentration of sFlt‐1 protein. Intriguingly, sFlt‐1‐loaded exosomes showed marked anti‐tumor activity by inhibiting the growth of NCI‐H69 tumor xenografts. CD31 staining revealed that sFlt‐1‐loaded exosomes significantly reduced the vascular density of experimental mice. sFlt‐1‐loaded exosomes markedly induced tumor apoptosis and inhibited tumor cell proliferation in mice.ConclusionExosomes from a SCLC cell line contain low levels of sFlt‐1 and significantly increased the migration of HUVECs. SFlt‐1‐enriched exosomes can inhibit NCI‐H69‐exo‐induced HUVEC migration. Exosomes enriched in sFlt‐1 have the potential to be effective therapeutic agents for SCLC.

Highlights

  • Small cell lung cancer (SCLC) is a lethal tumor accounting for approximately 15% of all lung malignancies, and the five-year survival rate is less than 7%.1,2 SCLC is typified by rapid tumor proliferation, high vascularity, frequent relapse, early metastatic dissemination, and poor prognosis

  • Transmission electron microscopy (TEM) analysis and nanoparticle tracking analysis (NTA), both methods revealed that NCI-H69-exosomes (NCI-H69-exo) and BEAS-2B-exosomes (BEAS-2B-exo) exhibited a typical cup-shaped appearance and ranged in diameter from 30 to 150 nm, consistent with the characteristics of exosomes reported by previous studies (Fig 1a,b)

  • We first explored the effect of exosomes derived from NCI-H69 and BEAS-2B cells on angiogenesis, to better understand the role of exosomes derived from SCLC cells

Read more

Summary

Introduction

Small cell lung cancer (SCLC) is a lethal tumor accounting for approximately 15% of all lung malignancies, and the five-year survival rate is less than 7%.1,2 SCLC is typified by rapid tumor proliferation, high vascularity, frequent relapse, early metastatic dissemination, and poor prognosis. SFlt-1-enriched exosomes inhibit the ECs migration progressive or recurrent SCLC; approval is based on three phase III trials, but the efficacy of topotecan is limited.[5,6,7] Therapeutic regimens for SCLC patients have remained unchanged for 30 years, resulting in the designation of SCLC as a recalcitrant cancer.[8,9] Angiogenesis is considered to be an important step in tumor growth and development of SCLC in vivo. We explored the effects of these exosomes on HUVE cell proliferation and migration in vitro.To verify sFlt-1-loaded exosomes suppress the tumor growth in vivo,we established subcutaneous xenografts in nude mice using the NCI-H69 cell line. Exosomes enriched in sFlt-1 have the potential to be effective therapeutic agents for SCLC

Objectives
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call