Influence of IL-8 on the epithelial–mesenchymal transition and the tumor microenvironment

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References

• 1  Kalluri R, Weinberg RA. The basics of epithelial–mesenchymal transition. J. Clin. Invest.119(6),1420–1428 (2009).▪ A comprehensive review of the role of the epithelial–mesenchymal transition (EMT) in normal and pathological conditions.
  Medline CASGoogle Scholar
• 2  Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat. Rev. Cancer9(4),265–273 (2009).
  Medline CASGoogle Scholar
• 3  Nieto MA. The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu. Rev. Cell Dev. Biol.27,347–376 (2011).
  Medline CASGoogle Scholar
• 4  Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat. Rev. Cancer2(6),442–454 (2002).
  Medline CASGoogle Scholar
• 5  Fernando RI, Litzinger M, Trono P, Hamilton DH, Schlom J, Palena C. The T-box transcription factor brachyury promotes epithelial–mesenchymal transition in human tumor cells. J. Clin. Invest.120(2),533–544 (2010).▪ Describes the T-box transcription factor as a regulator of EMT in human carcinomas.
  Medline CASGoogle Scholar
• 6  Vega S, Morales AV, Ocana OH, Valdes F, Fabregat I, Nieto MA. Snail blocks the cell cycle and confers resistance to cell death. Genes Dev.18(10),1131–1143 (2004).
  Medline CASGoogle Scholar
• 7  Kurrey NK, Jalgaonkar SP, Joglekar AV et al. Snail and Slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells27(9),2059–2068 (2009).
  Medline CASGoogle Scholar
• 8  Gupta PB, Onder TT, Jiang G et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell138(4),645–659 (2009).
  Medline CASGoogle Scholar
• 9  Thomson S, Buck E, Petti F et al. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res.65(20),9455–9462 (2005).
  Medline CASGoogle Scholar
• 10  Guarino M, Rubino B, Ballabio G. The role of epithelial–mesenchymal transition in cancer pathology. Pathology39(3),305–318 (2007).
  Medline CASGoogle Scholar
• 11  Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA. A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clin. Cancer Res.13(23),7003–7011 (2007).
  Medline CASGoogle Scholar
• 12  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.68(10),3645–3654 (2008).
  Medline CASGoogle Scholar
• 13  Sawada K, Mitra AK, Radjabi AR et al. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res.68(7),2329–2339 (2008).
  Medline CASGoogle Scholar
• 14  Sarrio D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J. Epithelial–mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res.68(4),989–997 (2008).
  Medline CASGoogle Scholar
• 15  Mani SA, Guo W, Liao MJ et al. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell133(4),704–715 (2008).▪▪ First paper describing a link between tumor EMT and the acquisition of characteristics associated with cancer stem cells.
  Medline CASGoogle Scholar
• 16  Creighton CJ, Li X, Landis M et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc. Natl Acad. Sci. USA106(33),13820–13825 (2009).▪ Describes the association between cancer stem cells and tumor EMT in vivo.
  Medline CASGoogle Scholar
• 17  Wang Y, Ngo VN, Marani M et al. Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells. Oncogene29(33),4658–4670 (2010).
  Medline CASGoogle Scholar
• 18  Sabbah M, Emami S, Redeuilh G et al. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist. Updat.11(4–5),123–151 (2008).
  Medline CASGoogle Scholar
• 19  Moustakas A, Heldin CH. Signaling networks guiding epithelial–mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci.98(10),1512–1520 (2007).
  Medline CASGoogle Scholar
• 20  Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat. Rev. Mol. Cell Biol.7(2),131–142 (2006).
  Medline CASGoogle Scholar
• 21  Nannuru KC, Singh RK. Tumor–stromal interactions in bone metastasis. Curr. Osteoporos Rep.8(2),105–113 (2010).
  MedlineGoogle Scholar
• 22  Sansone P, Storci G, Tavolari S et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J. Clin. Invest.117(12),3988–4002 (2007).
  Medline CASGoogle Scholar
• 23  Mathias RA, Wang B, Ji H et al. Secretome-based proteomic profiling of Ras-transformed MDCK cells reveals extracellular modulators of epithelial–mesenchymal transition. J. Proteome Res.8(6),2827–2837 (2009).
  Medline CASGoogle Scholar
• 24  Scheel C, Eaton EN, Li SH et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell145(6),926–940 (2011).
  Medline CASGoogle Scholar
• 25  Gregory PA, Bracken CP, Smith E et al. An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial–mesenchymal transition. Mol. Biol. Cell22(10),1686–1698 (2011).
  Medline CASGoogle Scholar
• 26  Oft M, Heider KH, Beug H. TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr. Biol.8(23),1243–1252 (1998).
  Medline CASGoogle Scholar
• 27  Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat. Genet.29(2),117–129 (2001).
  Medline CASGoogle Scholar
• 28  Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene24(37),5764–5774 (2005).
  Medline CASGoogle Scholar
• 29  Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y. Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell15(3),195–206 (2009).
  Medline CASGoogle Scholar
• 30  Jechlinger M, Grunert S, Tamir IH et al. Expression profiling of epithelial plasticity in tumor progression. Oncogene22(46),7155–7169 (2003).
  Medline CASGoogle Scholar
• 31  Sullivan NJ, Sasser AK, Axel AE et al. Interleukin-6 induces an epithelial–mesenchymal transition phenotype in human breast cancer cells. Oncogene28(33),2940–2947 (2009).
  Medline CASGoogle Scholar
• 32  Gonzalez-Moreno O, Lecanda J, Green JE et al. VEGF elicits epithelial–mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop. Exp. Cell Res.316(4),554–567 (2009).
  MedlineGoogle Scholar
• 33  Kishimoto T. IL-6: from its discovery to clinical applications. Int. Immunol.22(5),347–352 (2010).
  Medline CASGoogle Scholar
• 34  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. Targets11(5),613–624 (2007).
  Medline CASGoogle Scholar
• 35  Sasser AK, Sullivan NJ, Studebaker AW, Hendey LF, Axel AE, Hall BM. Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J.21(13),3763–3770 (2007).
  Medline CASGoogle Scholar
• 36  Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat. Rev. Cancer6(10),764–775 (2006).
  Medline CASGoogle Scholar
• 37  Ota I, Li XY, Hu Y, Weiss SJ. Induction of a MT1-MMP and MT2-MMP-dependent basement membrane transmigration program in cancer cells by Snail1. Proc. Natl Acad. Sci. USA106(48),20318–20323 (2009).
  Medline CASGoogle Scholar
• 38  Lochter A, Galosy S, Muschler J, Freedman N, Werb Z, Bissell MJ. Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J. Cell Biol.139(7),1861–1872 (1997).
  Medline CASGoogle Scholar
• 39  Przybylo JA, Radisky DC. Matrix metalloproteinase-induced epithelial–mesenchymal transition: tumor progression at Snail’s pace. Int. J. Biochem. Cell Biol.39(6),1082–1088 (2007).
  Medline CASGoogle Scholar
• 40  Illman SA, Lehti K, Keski-Oja J, Lohi J. Epilysin (MMP-28) induces TGF-beta mediated epithelial to mesenchymal transition in lung carcinoma cells. J. Cell Sci.119(Pt 18),3856–3865 (2006).
  Medline CASGoogle Scholar
• 41  Cano A, Perez-Moreno MA, Rodrigo I et al. The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol.2(2),76–83 (2000).
  Medline CASGoogle Scholar
• 42  Blanco MJ, Moreno-Bueno G, Sarrio D et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene21(20),3241–3246 (2002).
  Medline CASGoogle Scholar
• 43  Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J. Cell Sci.116(Pt 3),499–511 (2003).
  Medline CASGoogle Scholar
• 44  Shih JY, Tsai MF, Chang TH et al. Transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma. Clin. Cancer Res.11(22),8070–8078 (2005).
  Medline CASGoogle Scholar
• 45  Yang J, Mani SA, Donaher JL et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell117(7),927–939 (2004).
  Medline CASGoogle Scholar
• 46  Kwok WK, Ling MT, Lee TW et al. Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target. Cancer Res.65(12),5153–5162 (2005).
  Medline CASGoogle Scholar
• 47  Herrmann BG, Labeit S, Poustka A, King TR, Lehrach H. Cloning of the T gene required in mesoderm formation in the mouse. Nature343(6259),617–622 (1990).
  Medline CASGoogle Scholar
• 48  Fernando RI, Castillo MD, Litzinger M, Hamilton DH, Palena C. IL-8 signaling plays a critical role in the epithelial–mesenchymal transition of human carcinoma cells. Cancer Res.71(15),5296–5306 (2011).▪▪ First paper describing the ability of IL-8 signaling to induce and maintain brachyury-induced EMT in human breast carcinoma cell lines.
  Medline CASGoogle Scholar
• 49  Coppe JP, Patil CK, Rodier F et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol.6(12),2853–2868 (2008).
  Medline CASGoogle Scholar
• 50  Luboshits G, Shina S, Kaplan O et al. Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res.59(18),4681–4687 (1999).
  Medline CASGoogle Scholar
• 51  Dannenmann C, Shabani N, Friese K, Jeschke U, Mylonas I, Bruning A. The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERbeta, and enhances expression of oncogenic cytokine GRO. Cancer Biol. Ther.7(9),1460–1467 (2008).
  Medline CASGoogle Scholar
• 52  Ancrile B, Lim KH, Counter CM. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev.21(14),1714–1719 (2007).
  Medline CASGoogle Scholar
• 53  Yoshimura T, Matsushima K, Oppenheim JJ, Leonard EJ. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J. Immunol.139(3),788–793 (1987).
  Medline CASGoogle Scholar
• 54  Skov L, Beurskens FJ, Zachariae CO et al. IL-8 as antibody therapeutic target in inflammatory diseases: reduction of clinical activity in palmoplantar pustulosis. J. Immunol.181(1),669–679 (2008).
  Medline CASGoogle Scholar
• 55  Larsen CG, Anderson AO, Oppenheim JJ, Matsushima K. Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumour necrosis factor. Immunology68(1),31–36 (1989).
  Medline CASGoogle Scholar
• 56  Desbaillets I, Diserens AC, Tribolet N, Hamou MF, Van Meir EG. Upregulation of interleukin 8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis, and angiogenesis. J. Exp. Med.186(8),1201–1212 (1997).
  Medline CASGoogle Scholar
• 57  Xie K. Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev.12(4),375–391 (2001).
  Medline CASGoogle Scholar
• 58  Stillie R, Farooq SM, Gordon JR, Stadnyk AW. The functional significance behind expressing two IL-8 receptor types on PMN. J. Leukoc. Biol.86(3),529–543 (2009).
  Medline CASGoogle Scholar
• 59  Waugh DJ, Wilson C. The interleukin-8 pathway in cancer. Clin. Cancer Res.14(21),6735–6741 (2008).
  Medline CASGoogle Scholar
• 60  Gabellini C, Trisciuoglio D, Desideri M et al. Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. Eur. J. Cancer45(14),2618–2627 (2009).
  Medline CASGoogle Scholar
• 61  Bates RC, DeLeo MJ 3rd, Mercurio AM. The epithelial–mesenchymal transition of colon carcinoma involves expression of IL-8 and CXCR-1-mediated chemotaxis. Exp. Cell Res.299(2),315–324 (2004).
  Medline CASGoogle Scholar
• 62  Hwang WL, Yang MH, Tsai ML et al. SNAIL regulates interleukin-8 expression, stem cell-like activity, and tumorigenicity of human colorectal carcinoma cells. Gastroenterology141(1),279–291 (2011).
  Medline CASGoogle Scholar
• 63  Charafe-Jauffret E, Ginestier C, Iovino F et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res.69(4),1302–1313 (2009).▪▪ First paper describing the ability of IL-8 signaling to induce a cancer stem cell phenotype in human breast carcinoma cell lines.
  Medline CASGoogle Scholar
• 64  Ginestier C, Liu S, Diebel ME et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J. Clin. Invest.120(2),485–497 (2010).▪▪ Demonstrates the potential of treatment strategies targeting the IL-8–IL-8 receptor axis to target tumor cells with a cancer stem cell phenotype.
  Medline CASGoogle Scholar
• 65  Chang CJ, Chien Y, Lu KH et al. Oct4-related cytokine effects regulate tumorigenic properties of colorectal cancer cells. Biochem. Biophys. Res. Commun.415(2),245–251 (2011).
  Medline CASGoogle Scholar
• 66  Li A, Dubey S, Varney ML, Dave BJ, Singh RK. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J. Immunol.170(6),3369–3376 (2003).
  Medline CASGoogle Scholar
• 67  Yanagawa J, Walser TC, Zhu LX et al. Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma. Clin. Cancer Res.15(22),6820–6829 (2009).
  Medline CASGoogle Scholar
• 68  Mironchik Y, Winnard PT Jr, Vesuna F et al. Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer. Cancer Res.65(23),10801–10809 (2005).
  Medline CASGoogle Scholar
• 69  Ji H, Houghton AM, Mariani TJ et al. K-ras activation generates an inflammatory response in lung tumors. Oncogene25(14),2105–2112 (2006).
  Medline CASGoogle Scholar
• 70  Huh SJ, Liang S, Sharma A, Dong C, Robertson GP. Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development. Cancer Res.70(14),6071–6082 (2010).
  Medline CASGoogle Scholar
• 71  Gregory AD, Houghton AM. Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res.71(7),2411–2416 (2011).
  Medline CASGoogle Scholar
• 72  Schadendorf D, Moller A, Algermissen B, Worm M, Sticherling M, Czarnetzki BM. IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J. Immunol.151(5),2667–2675 (1993).
  Medline CASGoogle Scholar
• 73  De Larco JE, Wuertz BR, Rosner KA et al. A potential role for interleukin-8 in the metastatic phenotype of breast carcinoma cells. Am. J. Pathol.158(2),639–646 (2001).
  MedlineGoogle Scholar
• 74  Maxwell PJ, Gallagher R, Seaton A et al. HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells. Oncogene26(52),7333–7345 (2007).
  Medline CASGoogle Scholar
• 75  Chaffer CL, Brennan JP, Slavin JL, Blick T, Thompson EW, Williams ED. Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Res.66(23),11271–11278 (2006).
  Medline CASGoogle Scholar
• 76  Bukholm IK, Nesland JM, Borresen-Dale AL. Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-catenin, in metastatic tissue from breast cancer patients [see comments]. J. Pathol.190(1),15–19 (2000).
  Medline CASGoogle Scholar
• 77  Mian BM, Dinney CP, Bermejo CE et al. Fully human anti-interleukin 8 antibody inhibits tumor growth in orthotopic bladder cancer xenografts via down-regulation of matrix metalloproteases and nuclear factor-kappaB. Clin. Cancer Res.9(8),3167–3175 (2003).
  Medline CASGoogle Scholar
• 78  Sparmann A, Bar-Sagi D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell6(5),447–458 (2004).
  Medline CASGoogle Scholar
• 79  Reka AK, Kurapati H, Narala VR et al. Peroxisome proliferator-activated receptor-gamma activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial–mesenchymal transition. Mol. Cancer Ther.9(12),3221–3232 (2010).
  Medline CASGoogle Scholar
• 80  Palena C, Polev DE, Tsang KY et al. The human T-box mesodermal transcription factor brachyury is a candidate target for T-cell-mediated cancer immunotherapy. Clin. Cancer Res.13(8),2471–2478 (2007).▪ Describes the potential use of immunotherapy to target tumor cells undergoing EMT via cancer vaccine approaches against the T-box transcription factor brachyury.
  Medline CASGoogle Scholar