Effect and Mechanism of Hyperhomocysteine on Metastasis of Nasopharyngeal Carcinoma through EMT

Objective: To investigate the effect of Homocysteine on the invasion and migration capability in nasopharyngeal carcinoma CNE-2 cells and to explore the possible mechanism. Methods: After high concentration HCY treatment, the cell morphology of CNE-2 cells was evaluated by phase-contrast microscopy, the colony forming ability was detected by soft agar cloning experiment, and the invasion and migration capability was reflexed by invasion and migration experiments. Moreover, the mechanism was also investigated. Results: HCY exposure led to the transformation of the cobblestone-like cells CNE-2 to spindle-like, fibroblastic cells, accompanied by enhanced colony forming ability and invasion and migration capability. Western blot showed that the mesenchymal marker was up-regulated and the epithelial marker was down-regulated after HCY treatment, which implied that HCY might work through EMT to promote the malignant transformation of CNE-2 cells.

[1]  Kouichi Miura,et al.  Homocysteine supplementation ameliorates steatohepatitis induced by a choline‐deficient diet in mice , 2018, Hepatology research : the official journal of the Japan Society of Hepatology.

[2]  G. Chrysant,et al.  The current status of homocysteine as a risk factor for cardiovascular disease: a mini review , 2018, Expert review of cardiovascular therapy.

[3]  Youngjoo Kwon,et al.  Causes of hyperhomocysteinemia and its pathological significance , 2018, Archives of Pharmacal Research.

[4]  T. Zhou,et al.  Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial–mesenchymal transition and metastasis , 2017, Cell Death & Disease.

[5]  B. Huppertz,et al.  Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy , 2016, Angiogenesis.

[6]  Shih-Chien Huang,et al.  High homocysteine is associated with increased risk of colorectal cancer independently of oxidative stress and antioxidant capacities. , 2014, Clinical nutrition.

[7]  V. Kutala,et al.  Impact of Hyperhomocysteinemia on Breast Cancer Initiation and Progression: Epigenetic Perspective , 2014, Cell Biochemistry and Biophysics.

[8]  C. Qian,et al.  The prevalence and prevention of nasopharyngeal carcinoma in China , 2011, Chinese journal of cancer.

[9]  J. Shao,et al.  Epstein-Barr Virus-Encoded LMP2A Induces an Epithelial–Mesenchymal Transition and Increases the Number of Side Population Stem-like Cancer Cells in Nasopharyngeal Carcinoma , 2010, PLoS pathogens.

[10]  Raghu Kalluri,et al.  The basics of epithelial-mesenchymal transition. , 2009, The Journal of clinical investigation.

[11]  J. Armand,et al.  Optimal management of nasopharyngeal carcinoma , 2004, Current opinion in oncology.

[12]  D. Fuchs,et al.  Serum folate and homocysteine levels in head and neck squamous cell carcinoma , 2002, Cancer.