|
|
Effects of serum exosomes in intermittent hypoxia mice on epithelial-mesenchymal transformation, invasion and metastasis of Lewis lung cancer cells |
CHENG Linjie YAO Qiaoling#br# |
Department of Physiology, School of Basic Medical Sciences, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China |
|
|
Abstract Objective To investigate the effect of serum exosomes in intermittent hypoxia (IH) mice on epithelial-mesenchymal transition, invasion and metastasis of Lewis lung cancer cells (LLC). Methods Eighty C57BL/6J male mice, 7-8 weeks old, weighing 22-25 g were selected. Two mice with similar body weight were randomly divided into indoor air group (RA) and IH group. The difference in average body weight of mice between the two groups was ≤2 g, with 40 mice in each group. In the IH group, IH stimulation was performed for one minute per cycle, and the oxygen partial pressure was changed from (6±1)%/30 s to (21±1)%/30 s, 12 h/d, for four consecutive weeks. Mice in RA group were housed in ordinary cages. Extraction of exosomes from mouse serum; cell viability was detected by CCK-8 method; Transwell assay and cell scratch assay were used to detect cell invasion and migration ability; Western blot was used to detect the protein expression levels of E-cadherin, N-cadherin, and matrix metalloproteinase 9 (MMP-9). Results After incubating LLC cells with mouse serum exosomes, the number of viable cells in the IH group was higher than that in the RA group, and the difference was highly statistically significant (P < 0.01); the ability of cell invasion and migration in the IH group was higher than that in the RA group, and the difference was highly statistically significant (P < 0.01); the expression level of E-cadherin in the IH group was lower than that in the RA group, and the difference was statistically significant (P < 0.05); the expression level of N-cadherin in the IH group was higher than that in the RA group, and the difference was statistically significant (P < 0.05); therei was no significant difference in the expression levels of MMP-9 between the two groups (P > 0.05). Conclusion Serum exosomes from IH mice may induce EMT and invasion and metastasis of LLC cells.
|
|
|
|
|
[1] Prabhakar NR,Peng YJ,Nanduri J. Hypoxia-inducible factors and obstructive sleep apnea [J]. J Clin Invest,2020, 130(10):5042-5051.
[2] Nieto FJ,Peppard PE,Young T,et al. Sleep-disordered breathing and cancer mortality:results from the Wisconsin Sleep Cohort Study [J]. Am J Respir Crit Care Med,2012, 186(2):190-194.
[3] Campos-Rodriguez F,Martinez-Garcia MA,Martinez M,et al. Association between obstructive sleep apnea and cancer incidence in a large multicenter spanish cohort [J]. Am J Respir Crit Care Med,2013,187(1):99-105.
[4] Li W,Huang K,Wen F,et al. Intermittent hypoxia-induced downregulation of microRNA-320b promotes lung cancer tumorigenesis by increasing CDT1 via USP37 [J]. Mol Ther Nucleic Acids,2021,24:528-541.
[5] Xie F,Zhou X,Fang M,et al. Extracellular Vesicles in Cancer Immune Microenvironment and Cancer Immunot-herapy [J]. Adv Sci (Weinh),2019,6(24):1901779.
[6] Lu R,Zhou Q,Ju L,et al. Upregulation of TRIP13 promotes the malignant progression of lung cancer via the EMT pathway [J]. Oncol Rep,2021,46(2):172.
[7] Shu J,Wang L,Han F,et al. BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer [J]. Biomed Res Int,2019,2019:5937635.
[8] Wang X,Chen Q,Zhang X,et al. Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer:preparation and in vitro/in vivo studies [J]. Int J Nanomedicine,2018,13:4641-4659.
[9] Zhang X,Sai B,Wang F,et al. Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT [J]. Mol Cancer,2019,18(1):40.
[10] Yao Q,Shin MK,Jun JC,et al. Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues [J]. J Lipid Res,2013,54(4):1058-1065.
[11] Randerath W,Bonsignore MR,Herkenrath S. Obstructive sleep apnoea in acute coronary syndrome [J]. Eur Respir Rev,2019,28(153):1-16.
[12] Li M,Li X,Lu Y. Obstructive Sleep Apnea Syndrome and Metabolic Diseases [J]. Endocrinology,2018,159(7):2670-2675.
[13] Ji T,Li X,Chen J,et al. Brain Function in Children with Obstructive Sleep Apnea:A Resting-State fMRI Study [J]. Sleep,2021,44(8):zsab047.
[14] Ma Y,Yuwen D,Chen J,et al. Exosomal Transfer of Cisplatin-Induced miR-425-3p Confers Cisplatin Resistance in NSCLC Through Activating Autophagy [J]. Int J Nanomedicine,2019,14:8121-8132.
[15] Deng ZT,Wang JQ,Xiao Y,et al. Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-β-induced neurotoxicity [J]. Theranostics,2021, 11(9):4351-4362.
[16] Yang XX,Sun C,Wang L,et al. New insight into isolation,identification techniques and medical applications of exosomes [J]. J Control Release,2019,308:119-129.
[17] Zhang Y,Liu Z,Li S,et al. Upregulation of E-cadherin in bronchoalveolar lavage fluid-derived exosomes in patients with lung cancer [J]. Thorac Cancer,2020,11(1):41-47.
[18] Navarro A,Molins L,Marrades RM,et al. Exosome Analysis in Tumor-Draining Pulmonary Vein Identifies NSCLC Patients with Higher Risk of Relapse after Curative Surgery [J]. Cancers (Basel),2019,11(2):249.
[19] Li HL,Li QY,Jin MJ,et al. A review:hippo signaling pathway promotes tumor invasion and metastasis by regulating target gene expression [J]. J Cancer Res Clin Oncol,2021,147(6):1569-1585.
[20] Hunyor I,Cook KM. Models of intermittent hypoxia and obstructive sleep apnea:molecular pathways and their contribution to cancer [J]. Am J Physiol Regul Integr Comp Physiol,2018,315(4):R669-R687.
[21] Kang HS,Kwon HY,Kim IK,et al. Intermittent hypoxia exacerbates tumor progression in a mouse model of lung cancer [J]. Sci Rep,2020,10(1):1854.
[22] Ashrafizadeh M,Shahinozzaman M,Orouei S,et al. Crosstalk of Long Non-coding RNAs and EMT:Searching the Missing Pieces of an Incomplete Puzzle for Lung Cancer Therapy [J]. Curr Cancer Drug Targets,2021,21(8):640-665.
[23] Li Q,Zhou ZW,Duan W,et al. Inhibiting the redox function of APE1 suppresses cervical cancer metastasis via disengagement of ZEB1 from E-cadherin in EMT [J]. J Exp Clin Cancer Res,2021,40(1):220.
[24] Labernadie A,Kato T,Brugués A. et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion [J]. Nat Cell Biol,2017,19(3):224-237.
[25] 赵天源,张艳敏,常延河.非小细胞肺癌组织中HAb18G、MMP-9和MMP-2表达与预后的相关性[J].临床与实验病理学杂志,2020,36(7):819-822. |
|
|
|