Non-contact Co-culture with Human Vascular Endothelial Cells Promotes Epithelial-to-mesenchymal Transition of Cervical Cancer SiHa Cells by Activating the NOTCH1/LOX/SNAIL Pathway

Overview

Journal Cell Mol Biol Lett

Publisher Biomed Central

Specialties Biochemistry
Cell Biology
Molecular Biology

Date 2019 Jun 18

PMID 31205475

Citations 11

Authors

Jinghua Ou

Defeng Guan

Yongxiu Yang

Affiliations

Soon will be listed here.

Abstract

Background: The aim of this study was to investigate the effect of human umbilical vein endothelial cells on epithelial-to-mesenchymal transition of the cervical cancer cell line SiHa by studying the Notch1/lysyl oxidase (LOX)/SNAIL1 pathway.

Methods: Monocultures of SiHa cells, SiHa cells containing a control sequence, and -silenced SiHa cells, as well as co-cultures of human umbilical vein endothelial cells with SiHa cells and -silenced SiHa cells, were established. The invasiveness of SiHa cells in each group was evaluated using a Transwell assay. The mRNA levels of E-cadherin and vimentin were detected using quantitative real-time polymerase chain reaction. The expression levels of the matrix metalloproteinases MMP-2 and MMP-9 were determined in SiHa cells using an immunofluorescence assay and the protein activity was detected by gelatin zymography. Changes in LOX, SNAIL1 and NOTCH1 expression in the SiHa cells in each group were detected using western blotting.

Results: Compared with monocultured SiHa cells, co-cultured SiHa cells showed a significant increase in their invasiveness and expression levels of vimentin, as well as of NOTCH 1, LOX, and SNAIL1, whereas their expression of E-cadherin was significantly reduced and protein activities of MMP-2 and MMP-9 were increased. Compared with SiHa, mono- and co-cultured -silenced SiHa cells showed significant reductions in their invasiveness and expression levels of vimentin, NOTCH 1, LOX, and SNAIL1, whereas their expression of E-cadherin significantly increased and protein activities of MMP-2 and MMP-9 decreased.

Conclusion: Co-culture with human umbilical vein endothelial cells promoted the epithelial-to-mesenchymal transition of SiHa cells by activating the NOTCH1/LOX/SNAIL1 pathway in SiHa cells, which enhanced their invasive and metastatic capacities. The results of this study may provide a new perspective on cervical cancer metastasis and a theoretical basis for clinical treatment.

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References

Folkman J . Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2003; 29(6 Suppl 16):15-8. DOI: 10.1053/sonc.2002.37263. View

Yilmaz M, Christofori G . EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009; 28(1-2):15-33. DOI: 10.1007/s10555-008-9169-0. View

Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y . Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell. 2009; 15(3):195-206. DOI: 10.1016/j.ccr.2009.01.023. View

De Craene B, Berx G . Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013; 13(2):97-110. DOI: 10.1038/nrc3447. View

Torre L, Siegel R, Ward E, Jemal A . Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev. 2015; 25(1):16-27. DOI: 10.1158/1055-9965.EPI-15-0578. View

Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F . PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation. Mol Cancer. 2016; 15:3. PMC: 4704385. DOI: 10.1186/s12943-015-0490-2. View

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

Shang C, Zhu W, Liu T, Wang W, Huang G, Huang J . Characterization of long non-coding RNA expression profiles in lymph node metastasis of early-stage cervical cancer. Oncol Rep. 2016; 35(6):3185-97. PMC: 4869942. DOI: 10.3892/or.2016.4715. View

McDonald P, Chafe S, Dedhar S . Overcoming Hypoxia-Mediated Tumor Progression: Combinatorial Approaches Targeting pH Regulation, Angiogenesis and Immune Dysfunction. Front Cell Dev Biol. 2016; 4:27. PMC: 4814851. DOI: 10.3389/fcell.2016.00027. View

10.

Zhang L, Zhan X, Yan D, Wang Z . Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1. Int J Gynecol Cancer. 2016; 26(5):810-6. DOI: 10.1097/IGC.0000000000000694. View

11.

Korniluk A, Koper O, Kemona H, Dymicka-Piekarska V . From inflammation to cancer. Ir J Med Sci. 2016; 186(1):57-62. PMC: 5323483. DOI: 10.1007/s11845-016-1464-0. View

12.

Zhao X, Liu H, Li J, Liu X . Endothelial progenitor cells promote tumor growth and progression by enhancing new vessel formation. Oncol Lett. 2016; 12(2):793-799. PMC: 4950911. DOI: 10.3892/ol.2016.4733. View

13.

Wardak S . Human Papillomavirus (HPV) and cervical cancer. Med Dosw Mikrobiol. 2017; 68(1):73-84. View

14.

Zhou W, Wang Q, Xu Y, Jiang J, Guo J, Yu H . RMP promotes epithelial-mesenchymal transition through NF-κB/CSN2/Snail pathway in hepatocellular carcinoma. Oncotarget. 2017; 8(25):40373-40388. PMC: 5522250. DOI: 10.18632/oncotarget.16177. View

15.

Ali A, Kim S, Kim M, Choi M, Kang S, Cho G . O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. Mol Cells. 2017; 40(7):476-484. PMC: 5547217. DOI: 10.14348/molcells.2017.2309. View

16.

Wu L, Han L, Zhou C, Wei W, Chen X, Yi H . TGF-β1-induced CK17 enhances cancer stem cell-like properties rather than EMT in promoting cervical cancer metastasis via the ERK1/2-MZF1 signaling pathway. FEBS J. 2017; 284(18):3000-3017. DOI: 10.1111/febs.14162. View

17.

Liu P, Ma S, Liu H, Han H, Wang S . HCFU inhibits cervical cancer cells growth and metastasis by inactivating Wnt/β-catenin pathway. J Cell Biochem. 2017; . DOI: 10.1002/jcb.26570. View

18.

Chen H, Liu W, Wang B, Zhang Z . In Situ Analysis of Interactions between Fibroblast and Tumor Cells for Drug Assays with Microfluidic Non-Contact Co-Culture. Micromachines (Basel). 2018; 9(12). PMC: 6316063. DOI: 10.3390/mi9120665. View

19.

Zagouras P, Stifani S, Blaumueller C, Carcangiu M, Artavanis-Tsakonas S . Alterations in Notch signaling in neoplastic lesions of the human cervix. Proc Natl Acad Sci U S A. 1995; 92(14):6414-8. PMC: 41528. DOI: 10.1073/pnas.92.14.6414. View

20.

Daniel B, Rangarajan A, Mukherjee G, Vallikad E, Krishna S . The link between integration and expression of human papillomavirus type 16 genomes and cellular changes in the evolution of cervical intraepithelial neoplastic lesions. J Gen Virol. 1997; 78 ( Pt 5):1095-101. DOI: 10.1099/0022-1317-78-5-1095. View