Background Icotinib has been widely used in patients with non-small cell lung cancer (NSCLC), and have significantly enhanced the overall survival rate of NSCLC patients. However, acquired drug resistance limits its clinical efficacy. Tumor cell-derived exosomes have been reported to participate in various biological processes, including tumor invasion, metastasis and drug resistance. Materials and methods In the present study, drug resistance was measured by MTT assay. Exosomes were extracted from the cell supernatant using ultracentrifugation and identified by exosomal marker. HCC827 cells were treated with exosomes derived from icotinib-resistant (IR) HCC827 to observe the invasion and migration of parent cells. The expression of exo-mRNA was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-PCR). In addition, 10 exo-mRNAs detecting from the plasma and bronchoalveolar lavage fluid (BALF) of NSCLC patients with icotinib treatment were used to establish a new drug resistant-warning formula. Results The oncogene MET into exosomes was identified from icotinib-resistant lung cancer cells, and this was also presented in exosomes in NSCLC patients diagnosed with cancer metastasis after icotinib treatment. The knockdown of MET in exosomes significantly decreased the ability of invasion and migration in HCC827 cells. Conclusion It was suggested that MET might be specifically package and transferred by exosomes to modify the invasion and migration ability of the surrounding icotinib-sensitive cells.

Background: Endometriosis (EMs) is the most common gynaecological disorder with its etiology and/or pathophysiology remains enigmatic. Recent studies showed that extracellular vesicles (EVs), exosomes in particular, play a critical role in developing various clinical disorders. However, the implication of exosomes in endometriosis progression has not been well elucidated.Method: The ectopic stromal cellular exosomes (eEVs) were assessed by transwell assay, scratch tests, tube formation assay, western blot, and qRT-PCR analysis. Protein expression profiles of exosomes in endometrial tissue and vaginal discharge collected from patients with EMS and healthy donors were analysed by Mass spectrometry. siRNA interference technology was used to inhibit the expression of exosomal protein for the functional analysis in in-vivo. Finally, in-vitro experiments were performed to validate the results that we observed in EMs mouse model.Results:In vitro, we discovered that eEVs improved NSC migratory potential by upregulating MMP9 expression and activity. eEVs also aided angiogenesis and elevated the expression of inflammatory cytokines in ovarian epithelial cells, according to our findings. Moesin (MSN) levels in ESC exosomes were substantially greater than in NSC exosomes (1.22e8±5.58e6 vs. 6.605e7±4.574e6, LFQ intensity), as shown by protein mass spectrometry and bioinformatics analysis. In ectopic stromal cells, ERa receptors stimulated the RhoA/Rock-2/MSN pathway. We discovered that downregulating exosomal moesin reduced NSC migration (about 3-fold change) and MMP9 expression (about 2-fold change). On the other hand, Exomsni inhibited angiogenesis and inflammatory cytokine release. In vivo the result of immunohistochemistry and immunofluorescence demonstrated that exosomal MSN substantially modified the expression of MM9, VEGFR and p-VEGFR in polyclonal lesions. In addition, we discovered an elevation in the expression of proinflammatory factors in the surrounding tissue.Conclusion: Exosomal MSN derived from ectopic stromal cells can contribute to endometriosis progression by mediating the construction of a “migration-vascularization-inflammation” loop in the ectopic environment.

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Background: Endometriosis (EMS) is the most common gynaecological disorder with its etiology and/or pathophysiology remains enigmatic. Recent studies showed that extracellular vesicles (EVs), exosomes namely, play a critical role in the development of various clinical disorders, including inflammatory disease and cancers. Previous studies revealed the role of exosomes as a potential biomarker in EMS. However, the implication of exosomes in the disease progression of EMS has not been well elucidated. Method: The biological function of ectopic exosomes (eEVs) was examined by Transwell assay, scratch tests, tube formation assay, western blot, and qRT-PCR analysis. Mass spectrometry analysis of the exosomes isolated from fresh EMS tissue and vaginal discharge obtained from patients with and without EMS used to identify differentially expressed protein in exosomes from ectopic stromal cells (ESCs) and normal endometrial stromal cells (NESCs). Gene knockdown was used to downregulate the expression of exosomal protein in in-vivo setting. Finally, in-vitro experiment confirmed the results that we observed in endometriosis (EMS) mouse model. Results: We found that eEVs increased the migration ability of NESCs) by up-regulating MMP9 expression. We also observed that eEVs facilitate angiogenesis, and induced the high expression of inflammatory cytokines in ovarian epithelial cells. Protein Mass spectrometry and bioinformatics analysis showed that Moesin (MSN) is highly expressed in eEVs. An abnormal high estrogen environment may up-regulate MSN expression in ectopic lesion. Downregulation of exosomal Moesin attenuated the migration capability of normal endometrium, inhibited angiogenesis, and reduced the expression of inflammatory cytokine. Moreover, we found that ectopic exosomes significantly increased the number and size of heterotopic foci in vivo. Also, we observed an increase in the size of vascular lumen, and upregulation of inflammatory factors expression in small intestine adjacent to the heterotopic foci. Conclusion: Exosomal MSN from ectopic stromal cells could contribute to the development of EMS by mediating the construction of a “migration-vascularization-inflammation” loop in ectopic environment.