The CCL2/CCR2 axis enhances IL-6-induced epithelial-mesenchymal transition by cooperatively activating STAT3-Twist signaling

Tumor Biology

Volumn 36, Issue 2, 2015, Pages 973-981

  Chen, Wei ^a   Gao, Qiang ^b   Han, Siqi ^c   Pan, Fei ^d   Fan, Wei ^e  

^a NAVY GENERAL HOSPITAL   (China)

^b THE SECOND AFFILIATED HOSPITAL OF HARBIN MEDICAL UNIVERSITY   (China)

^c JINLING HOSPITAL   (China)

^d CHINESE PLA GENERAL HOSPITAL   (China)

^e NANJING MEDICAL UNIVERSITY   (China)

Author keywords

CCL2; Coaction; Epithelial mesenchymal transition; IL 6; Metastasis; Tumor microenvironment

Indexed keywords

CHEMOKINE RECEPTOR CCR2; INTERLEUKIN 6; MONOCYTE CHEMOTACTIC PROTEIN 1; STAT3 PROTEIN; TRANSCRIPTION FACTOR SLUG; TRANSCRIPTION FACTOR TWIST; IL6 PROTEIN, HUMAN; NUCLEAR PROTEIN; STAT3 PROTEIN, HUMAN; TWIST1 PROTEIN, HUMAN;

ARTICLE; CELL MIGRATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; HUMAN CELL; NON SMALL CELL LUNG CANCER; POSITIVE FEEDBACK; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TUMOR ASSOCIATED LEUKOCYTE; TUMOR INVASION; TUMOR MICROENVIRONMENT; UPREGULATION; BIOSYNTHESIS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PATHOLOGY; PHOSPHORYLATION; TUMOR CELL LINE;

CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CHEMOKINE CCL2; EPITHELIAL-MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTERLEUKIN-6; NUCLEAR PROTEINS; PHOSPHORYLATION; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; TUMOR MICROENVIRONMENT; TWIST TRANSCRIPTION FACTOR;

EID: 84925483834     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1007/s13277-014-2717-z     Document Type: Article

References (34)

1. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68(10):3645–54.
2. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73.
3. Neel DS, Bivona TG. Secrets of drug resistance in NSCLC exposed by new molecular definition of EMT. Clin Cancer Res. 2013;19(1):3–5.
4. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.
5. Soltermann A, Tischler V, Arbogast S, Braun J, Probst-Hensch N, Weder W, et al. Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res. 2008;14(22):7430–7.
6. Thomson S, Petti F, Sujka-Kwok I, Mercado P, Bean J, Monaghan M, et al. A systems view of epithelial-mesenchymal transition signaling states. Clin Exp Metastasis. 2011;28(2):137–55.
7. Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 2009;15(5):416–28.
8. Kang Y, Massague J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 2004;118(3):277–9.
9. Sabbah M, Emami S, Redeuilh G, Julien S, Prevost G, Zimber A, et al. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat. 2008;11(4–5):123–51.
10. Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98(10):1512–20.
11. Scheel C, Eaton EN, Li SH, Chaffer CL, Reinhardt F, Kah KJ, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell. 2011;145(6):926–40.
12. Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, et al. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene. 2009;28(33):2940–7.
13. Gonzalez-Moreno O, Lecanda J, Green JE, Segura V, Catena R, Serrano D, et al. VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop. Exp Cell Res. 2010;316(4):554–67.
14. Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005;24(37):5764–74.
15. Heldin CH, Landstrom M, Moustakas A. Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol. 2009;21(2):166–76.
16. Rose-John S, Waetzig GH, Scheller J, Grotzinger J, Seegert D. The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin Ther Targets. 2007;11(5):613–24.
17. Rokavec M, Wu W, Luo JL. IL6-mediated suppression of miR-200c directs constitutive activation of inflammatory signaling circuit driving transformation and tumorigenesis. Mol Cell. 2012;45(6):777–89.
18. Chang CH, Hsiao CF, Yeh YM, Chang GC, Tsai YH, Chen YM, et al. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy. Int J Cancer. 2013;132(9):1977–85.
19. Zhao Z, Cheng X, Wang Y, Han R, Li L, Xiang T, et al. Metformin inhibits the IL-6-induced epithelial-mesenchymal transition and lung adenocarcinoma growth and metastasis. PLoS One. 2014;9(4):e95884.
20. Yadav A, Kumar B, Datta J, Teknos TN, Kumar P. IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res. 2011;9(12):1658–67.
21. Schweizer A, Dejager S, Bosi E. Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Obes Metab. 2009;11(8):804–12.
22. Kudo-Saito C, Shirako H, Ohike M, Tsukamoto N, Kawakami Y. CCL2 is critical for immunosuppression to promote cancer metastasis. Clin Exp Metastasis. 2013;30(4):393–405.
23. Izumi K, Fang LY, Mizokami A, Namiki M, Li L, Lin WJ, et al. Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation. EMBO Mol Med. 2013;5(9):1383–401.
24. Albini A, Magnani E, Noonan DM. The tumor microenvironment: biology of a complex cellular and tissue society. Q J Nucl Med Mol Imaging. 2010;54(3):244–8.
25. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331(6024):1559–64.
26. Grivennikov SI, Karin M. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis. 2011;70 Suppl 1:i104–8.
27. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(11):798–809.
28. Zhang XW, Qin X, Qin CY, Yin YL, Chen Y, Zhu HL. Expression of monocyte chemoattractant protein-1 and CC chemokine receptor 2 in non-small cell lung cancer and its significance. Cancer Immunol Immunother. 2013;62(3):563–70.
29. Lu Y, Cai Z, Xiao G, Liu Y, Keller ET, Yao Z, et al. CCR2 expression correlates with prostate cancer progression. J Cell Biochem. 2007;101(3):676–85.
30. Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, et al. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000;96(1):34–40.
31. Lu X, Kang Y. Chemokine (C-C motif) ligand 2 engages CCR2+ stromal cells of monocytic origin to promote breast cancer metastasis to lung and bone. J Biol Chem. 2009;284(42):29087–96.
32. Zhou C, Liu J, Tang Y, Liang X. Inflammation linking EMT and cancer stem cells. Oral Oncol. 2012;48:1068–75.
33. Low-Marchelli JM, Ardi VC, Vizcarra EA, van Rooijen N, Quigley JP, Yang J. Twist1 induces CCL2 and recruits macrophages to promote angiogenesis. Cancer Res. 2013;73(2):662–71.
34. Cheng GZ, Zhang WZ, Sun M, Wang Q, Coppola D, Mansour M, et al. Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function. J Biol Chem. 2008;283(21):14665–73.