Relationship Between Overexpression of EML4-ALK Variant 1 and Inflammatory Moleculars and Immune Mediators Associated with Tumor Progression and Metastasis in BEAS-2B and H2126 Cells
American Journal of Clinical and Experimental Medicine
Volume 4, Issue 4, July 2016, Pages: 103-108
Received: Jun. 16, 2016; Published: Jun. 17, 2016
Views 4207      Downloads 120
Yang Chen, Department of Respiratory Medicine, 306th Hospital of PLA, Beijing, China
Ping Wang, Department of Respiratory Medicine, 306th Hospital of PLA, Beijing, China
Article Tools
Follow on us
The aim of this study was to investigate the relationship between overexpression of EML4-ALK and inflammatory factors about tumor progression and metastasis in a human bronchial epithelial cell (BEAS-2B) and a lung cancer cell (H2126). The recombinant plasmids with EML4-ALK variant 1 and EML4-ALK K589M (EML4-ALK variant 1 kinase inactive mutant) fusion gene were constructed and introduced into H2126 and BEAS-2B cells after transfection. The plasmid pcDNA3.1 was negative control. Subsequent, cell proliferation assay and scratch wound healing assay were used to examine the proliferation and invasion of BEAS-2B and H2126 cells after transfection. Finally, we analyzed 24 inflammatory moleculars and immune mediators associated with tumor progression and metastasis. Compared to the empty vector as control, the expression level of ALK was upregulated in BEAS-2B and H2126 cells after transfection the plasmid EML4-ALK variant 1 and plasmid EML4-ALK K589M. In vitro, EML4-ALK variant 1 promoted the proliferation and invasion ability of BEAS-2B and H2126 cells compared with EML4-ALK K589M and empty vector. The results of Q-PCR showed that factors more differentially expressed between both groups of BEAS-2B and H2126 cells were S100A8 and S100A9 after transfection EML4-ALK variant 1. In conclusion, an increased expression level in S100A8 and S100A9 by overexpression EML4-ALK variant 1 had a great biological interest because of their relation with tumor cell proliferation and migration.
EML4-ALK Variant 1, Proliferation, Migration, S100A8, S100A9
To cite this article
Yang Chen, Ping Wang, Relationship Between Overexpression of EML4-ALK Variant 1 and Inflammatory Moleculars and Immune Mediators Associated with Tumor Progression and Metastasis in BEAS-2B and H2126 Cells, American Journal of Clinical and Experimental Medicine. Vol. 4, No. 4, 2016, pp. 103-108. doi: 10.11648/j.ajcem.20160404.13
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan, 66(1):7-30. doi: 10.3322/caac.21332
Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012 Jul-Aug, 62(4): 220-241. doi: 10.3322/caac.21149
Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM. The global burden of cancer: priorities for prevention. Carcinogenesis. 2010 Jan, 31(1): 100–110. doi: 10.1093/carcin/bgp263
Ansari J, Shackelford RE, El-Osta H. Epigenetics in non-small cell lung cancer: from basics to therapeutics. Transl Lung Cancer Res. 2016 Apr, 5(2): 155-71. doi:10.21037/tlcr.2016.02.02
Gerber DE, Schiller JH. Maintenance chemotherapy for advanced non-small-cell lung cancer: new life for an old idea. J Clin Oncol. 2013 Mar 10, 31(8): 1009-1020. doi: 10.1200/JCO.2012.43.7459
Tran B, Dancey JE, Kamel-Reid S, McPherson JD, Bedard PL, Brown AM, Zhang T, Shaw P, Onetto N, Stein L, Hudson TJ, Neel BG, Siu LL. Cancer genomics: technology, discovery, and translation. J Clin Oncol. 2012 Feb 20, 3 0(6): 647-660. doi: 10.1200/JCO.2011.39.2316
Tsao AS, Scagliotti GV, Bunn PA Jr, Carbone DP, Warren GW, Bai C, de Koning HJ, Yousaf-Khan AU, McWilliams A, Tsao MS, Adusumilli PS, Rami-Porta R, Asamura H, Van Schil PE, Darling GE, Ramalingam SS, Gomez DR, Rosenzweig KE, Zimmermann S, Peters S, Ignatius Ou SH, Reungwetwattana T, Jänne PA, Mok TS, Wakelee HA, Pirker R, Mazières J, Brahmer JR, Zhou Y, Herbst RS, Papadimitrakopoulou VA, Redman MW, Wynes MW, Gandara DR, Kelly RJ, Hirsch FR, Pass HI. Scientific Advances in Lung Cancer 2015. J Thorac Oncol. 2016 May, 11(5): 613-38. doi: 10.1016/j.jtho.2016.03.012
Fukihara J, Watanabe N, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Hasegawa Y. Clinical predictors of response to EGFR tyrosine kinase inhibitors in patients with EGFR-mutant non-small cell lung cancer. Oncology. 2014, 86(2): 86-93. doi: 10.1159/000357129
Xie J, Zhang X. The Impact of Genomic Profiling for Novel Cancer Therapy-Recent Progress in Non-Small Cell Lung Cancer. J Genet Genomics. 2016 Jan 20, 43(1): 3-10. doi: 10.1016/j.jgg.2015.09.003
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007 Aug 2,448(7153):561-566.
Palmer RH, Vernersson E, Grabbe C, Hallberg B. Anaplastic lymphoma kinase: signaling in development and disease. Biochem J. 2009 May 27, 4 20(3): 345-361. doi: 10.1042/BJ20090387
Mano H. The EML4-ALK oncogene: targeting an essential growth driver in human cancer. Proc Jpn Acad Ser B Phys Biol Sci. 2015, 91(5): 193-201. doi: 10.2183/pjab.91.193
Horsman MR, Vaupel P. Pathophysiological Basis for the Formation of the Tumor Microenvironment. Front Oncol. 2016 Apr 12, 6: 66. doi: 10.3389/fonc.2016.00066
Albini A, Sporn MB. The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer. 2007 Feb, 7(2): 139-147.
Xing Y, Zhao S, Zhou BP, Mi J. Metabolic reprogramming of the tumour microenvironment. FEBS J. 2015 Oct, 282(20): 3892-8. doi: 10.1111/febs.13402
Morán T, Quiroga V, Gil Mde L, Vilà L, Pardo N, Carcereny E, Capdevila L, Muñoz-Mármol AM, Rosell R. Targeting EML4-ALK driven non-small cell lung cancer (NSCLC). Transl Lung Cancer Res. 2013 Apr, 2(2): 128-41. doi: 10.3978/j.issn.2218-6751.2013.03.04
Livak and Schmittgen: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods 25:402-408, 2001.
Choi YL, Takeuchi K, Soda M, Inamura K, Togashi Y, Hatano S, Enomoto M, Hamada T, Haruta H, Watanabe H, Kurashina K, Hatanaka H, Ueno T, Takada S, Yamashita Y, Sugiyama Y, Ishikawa Y, Mano H. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res. 2008 Jul 1, 68(13): 4971-4976. doi: 10.1158/0008-5472.CAN-07-6158
Wang H, Yuan J, Ma Z. A new target in non-small cell lung cancer: EML4-ALK fusion gene. Zhongguo Fei Ai Za Zhi. 2011 Jun, 14(6): 538-542. doi: 10.3779/j.issn.1009-3419.2011.06.11
Soda M, Takada S, Takeuchi K, Choi YL, Enomoto M, Ueno T, Haruta H, Hamada T, Yamashita Y, Ishikawa Y, Sugiyama Y, Mano H. A mouse model for EML4-ALK-positive lung cancer. Proc Natl Acad Sci USA. 2008 Dec 16,105(50):19893-19897. doi: 10.1073/pnas.0805381105
Goyette J, Geczy CL. Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids. 2011 Oct, 41(4): 821-842. doi: 10.1007/s00726-010-0528-0
Srikrishna G. S100A8 and S100A9: new insights into their roles in malignancy. J Innate Immun. 2012, 4(1): 31-40. doi: 10.1159/000330095
Arai K, Takano S, Teratani T, Ito Y, Yamada T, Nozawa R. S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast. Curr Cancer Drug Targets. 2008 Jun, 8(4): 243-252.
Başsorgun Cİ, Unal B, Erin N, Ozlük A, Uzun OC, Elpek GÖ. S100A8 and S100A9 Positive Cells in Colorectal Carcinoma: Clinicopathological Analysis. Gastroenterol Res Pract. 2014,2014:943175. doi: 10.1155/2014/943175
Lim SY, Yuzhalin AE, Gordon-Weeks AN, Muschel RJ. Tumor-infiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells. Oncogene. 2016 Apr 18. doi: 10.1038/onc.2016.107
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186