| Journal of Angiogenesis Research | |
| Specific tumor-stroma interactions of EBV-positive Burkitt's lymphoma cells in the chick chorioallantoic membrane | |
| Jörg Wilting1  Dieter Kube2  Frederike von Bonin2  Ana Covelo-Fernandez2  Jürgen Becker1  | |
| [1] Department of Anatomy and Cell Biology, University Medicine Goettingen, 37075 Goettingen, Germany;Department of Hematology and Oncology, University Medicine Goettingen, 37075 Goettingen, Germany | |
| 关键词: esVEGFR-2; VEGF-C; VEGF-A; Dissemination; Lymphatics; BL74; BL2B95; BL2; EBV; Burkitt's lymphoma; | |
| Others : 802106 DOI : 10.1186/2045-824X-4-3 |
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| received in 2012-01-26, accepted in 2012-03-09, 发布年份 2012 | |
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【 摘 要 】
Background
Burkitt's lymphoma (BL) is an aggressive Non-Hodgkin lymphoma. Epstein-Barr Virus (EBV) is able to transform B cells and is a causative infectious agent in BL. The precise role of EBV in lymphoma progression is still unclear. Most investigations have concentrated on cell autonomous functions of EBV in B cells. Functions of the local environment in BL progression have rarely been studied, mainly due to the lack of appropriate in vivo models. Therefore, we inoculated different human BL cell-lines onto the chorioallantoic membrane (CAM) of embryonic day 10 (ED10) chick embryos and re-incubated until ED14 and ED17.
Results
All cell-lines formed solid tumors. However, we observed strong differences in the behavior of EBV+ and EBV- cell-lines. Tumor borders of EBV+ cells were very fuzzy and numerous cells migrated into the CAM. In EBV- tumors, the borders were much better defined. In contrast to EBV- cells, the EBV+ cells induced massive immigration of chick leukocytes at the tumor borders and the development of granulation tissue with large numbers of blood vessels and lymphatics, although the expression of pro- and anti-angiogenic forms of Vascular Endothelial Growth Factors/receptors was the same in all BL cell-lines tested. The EBV+ cell-lines massively disseminated via the lymphatics and completely occluded them.
Conclusions
Our data suggest that the EBV+ cells attract pro-angiogenic leukocytes, which then induce secondary tumor-stroma interactions contributing to the progression of BL. We show that the CAM is a highly suitable in vivo model to study the differential behavior of BL cell-lines.
【 授权许可】
2012 Becker et al; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, et al.: Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 2008, 9:105-116.
- [2]Kaiser U, Uebelacker I, Abel U, Birkmann J, Trumper L, Schmalenberg H, Karakas T, Metzner B, Hossfeld DK, Bischoff HG, et al.: Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma. J Clin Oncol 2002, 20:4413-4419.
- [3]Wunderlich A, Kloess M, Reiser M, Rudolph C, Truemper L, Bittner S, Schmalenberg H, Schmits R, Pfreundschuh M, Loeffler M: Practicability and acute haematological toxicity of 2- and 3-weekly CHOP and CHOEP chemotherapy for aggressive non-Hodgkin's lymphoma: results from the NHL-B trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol 2003, 14:881-893.
- [4]Burkitt D: A Sarcoma Involving the jaws in African Children. Br J Surg 1958, 46:218-223.
- [5]Chene A, Donati D, Orem J, Mbidde ER, Kironde F, Wahlgren M, Bejarano MT: Endemic Burkitt's lymphoma as a polymicrobial disease: new insights on the interaction between Plasmodium falciparum and Epstein-Barr virus. Semin Cancer Biol 2009, 19:411-420.
- [6]Moormann AM, Chelimo K, Sumba PO, Tisch DJ, Rochford R, Kazura JW: Exposure to holoendemic malaria results in suppression of Epstein-Barr virus-specific T cell immunosurveillance in Kenyan children. J Infect Dis 2007, 195:799-808.
- [7]Bornkamm GW: Epstein-Barr virus and the pathogenesis of Burkitt's lymphoma: more questions than answers. Int J Cancer 2009, 124:1745-1755.
- [8]Macor P, Secco E, Zorzet S, Tripodo C, Celeghini C, Tedesco F: An update on the xenograft and mouse models suitable for investigating new therapeutic compounds for the treatment of B-cell malignancies. Curr Pharm Des 2008, 14:2023-2039.
- [9]Mironov VA, Gusev SA, Baradi AF: Mesothelial stomata overlying omental milky spots: scanning electron microscopic study. Cell Tissue Res 1979, 201:327-330.
- [10]Wang ZBML, LJ C: Recent advances in the research of lymphatic stomata. Anat Rec (Hoboken) 2007, 293:754-761.
- [11]Pals ST, de Gorter DJ, Spaargaren M: Lymphoma dissemination: the other face of lymphocyte homing. Blood 2007, 110:3102-3111.
- [12]Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J: Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol 1997, 150:815-821.
- [13]Roorda BD, Ter Elst A, Scherpen FJ, Meeuwsen-de Boer TG, Kamps WA, de Bont ES: VEGF-A promotes lymphoma tumour growth by activation of STAT proteins and inhibition of p27(KIP1) via paracrine mechanisms. Eur J Cancer 2010, 46:974-982.
- [14]Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA: Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci USA 1998, 95:548-553.
- [15]Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K: Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 1997, 276:1423-1425.
- [16]Oh SJ, Jeltsch MM, Birkenhager R, McCarthy JE, Weich HA, Christ B, Alitalo K, Wilting J: VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev Biol 1997, 188:96-109.
- [17]Tammela T, Alitalo K: Lymphangiogenesis: Molecular mechanisms and future promise. Cell 2010, 140:460-476.
- [18]Albuquerque RJ, Hayashi T, Cho WG, Kleinman ME, Dridi S, Takeda A, Baffi JZ, Yamada K, Kaneko H, Green MG, et al.: Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med 2009, 15:1023-1030.
- [19]Pavlakovic H, Becker J, Albuquerque R, Wilting J, Ambati J: Soluble VEGFR-2: an antilymphangiogenic variant of VEGF receptors. Ann N Y Acad Sci 2010, 1207(Suppl 1):E7-15.
- [20]Ganjoo KN, Moore AM, Orazi A, Sen JA, Johnson CS, An CS: The importance of angiogenesis markers in the outcome of patients with diffuse large B cell lymphoma: a retrospective study of 97 patients. J Cancer Res Clin Oncol 2008, 134:381-387.
- [21]Jorgensen JM, Sorensen FB, Bendix K, Nielsen JL, Funder A, Karkkainen MJ, Tainola T, Sorensen AB, Pedersen FS, D'Amore F: Expression level, tissue distribution pattern, and prognostic impact of vascular endothelial growth factors VEGF and VEGF-C and their receptors Flt-1, KDR, and Flt-4 in different subtypes of non-Hodgkin lymphomas. Leuk Lymphoma 2009, 50:1647-1660.
- [22]Kadowaki I, Ichinohasama R, Harigae H, Ishizawa K, Okitsu Y, Kameoka J, Sasaki T: Accelerated lymphangiogenesis in malignant lymphoma: possible role of VEGF-A and VEGF-C. Br J Haematol 2005, 130:869-877.
- [23]Pazgal I, Boycov O, Shpilberg O, Okon E, Bairey O: Expression of VEGF-C, VEGF-D and their receptor VEGFR-3 in diffuse large B-cell lymphomas. Leuk Lymphoma 2007, 48:2213-2220.
- [24]Salven P, Lymboussaki A, Heikkila P, Jaaskela-Saari H, Enholm B, Aase K, von Euler G, Eriksson U, Alitalo K, Joensuu H: Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. Am J Pathol 1998, 153:103-108.
- [25]Wroel T, Mazur G, Dziegiel P, Jelen M, Szuba A, Kuliczkowski K, Zabel M: Density of intranodal lymphatics and VEGF-C expression in B-cell lymphoma and reactive lymph nodes. Folia Histochem Cytobiol 2006, 44:43-47.
- [26]Becker J, Pavlakovic H, Ludewig F, Wilting F, Weich HA, Albuquerque R, Ambati J, Wilting J: Neuroblastoma progression correlates with downregulation of the lymphangiogenesis inhibitor sVEGFR-2. Clin Cancer Res 2010, 16:1431-1441.
- [27]Wilting J, Birkenhäger R, Eichmann A, Kurz H, Martiny-Baron G, Marme D, McCarthy JE, Christ B, Weich HA: VEGF121induces proliferation of vascular endothelial cells and expression of flk-1 without affecting lymphatic vessels of chorioallantoic membrane. Dev Biol 1996, 176:76-85.
- [28]Hagedorn M, Javerzat S, Gilges D, Meyre A, de Lafarge B, Eichmann A, Bikfalvi A: Accessing key steps of human tumor progression in vivo by using an avian embryo model. Proc Natl Acad Sci USA 2005, 102:1643-1648.
- [29]Murphy JB, Rous P: The Behavior of Chicken Sarcoma Implanted in the Developing Embryo. J Exp Med 1912, 15:119-132.
- [30]Weber WT, Mausner R: Migration patterns of avian embryonic bone marrow cells and their differentiation to functional T and B cells. Adv Exp Med Biol 1977, 88:47-59.
- [31]Szenberg A: Ontogeny of myelopoietic precursor cells in the chicken embryo. Adv Exp Med Biol 1977, 88:3-11.
- [32]Wong GK, Cavey MJ: Development of the liver in the chicken embryo. II. Erythropoietic and granulopoietic cells. Anat Rec 1993, 235:131-143.
- [33]Bucy RP, Chen CH, Cooper MD: Ontogeny of T cell receptors in the chicken thymus. J Immunol 1990, 144:1161-1168.
- [34]Masteller EL, Thompson CB: B cell development in the chicken. Poult Sci 1994, 73:998-1011.
- [35]Reynaud CA, Imhof BA, Anquez V, Weill JC: Emergence of committed B lymphoid progenitors in the developing chicken embryo. EMBO J 1992, 11:4349-4358.
- [36]Tartour E, Pere H, Maillere B, Terme M, Merillon N, Taieb J, Sandoval F, Quintin-Colonna F, Lacerda K, Karadimou A, et al.: Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev 2011, 30:83-95.
- [37]Shah KM, Young LS: Epstein-Barr virus and carcinogenesis: beyond Burkitt's lymphoma. Clin Microbiol Infect 2009, 15:982-988.
- [38]Klein G, Klein E, Kashuba E: Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes. Biochem Biophys Res Commun 2010, 396:67-73.
- [39]Baker PS, Gold KG, Lane KA, Bilyk JR, Katowitz JA: Orbital burkitt lymphoma in immunocompetent patients: a report of 3 cases and a review of the literature. Ophthal Plast Reconstr Surg 2009, 25:464-468.
- [40]Papoutsi M, Siemeister G, Weindel K, Tomarev SI, Kurz H, Schachtele C, Martiny-Baron G, Christ B, Marme D, Wilting J: Active interaction of human A375 melanoma cells with the lymphatics in vivo. Histochem Cell Biol 2000, 114:373-385.
- [41]Wilting J, Becker J, Buttler K, Weich HA: Lymphatics and inflammation. Curr Med Chem 2009, 16:4581-4592.
- [42]Kube D, Platzer C, von Knethen A, Straub H, Bohlen H, Hafner M, Tesch H: Isolation of the human interleukin 10 promoter. Characterization of the promoter activity in Burkitt's lymphoma cell lines. Cytokine 1995, 7:1-7.
- [43]Vockerodt M, Tesch H, Kube D: Epstein-Barr virus latent membrane protein-1 activates CD25 expression in lymphoma cells involving the NFkappaB pathway. Genes Immun 2001, 2:433-441.
- [44]McNagny KM, Pettersson I, Rossi F, Flamme I, Shevchenko A, Mann M, Graf T: Thrombomucin, a novel cell surface protein that defines thrombocytes and multipotent hematopoietic progenitors. J Cell Biol 1997, 138:1395-1407.
- [45]Sela S, Itin A, Natanson-Yaron S, Greenfield C, Goldman-Wohl D, Yagel S, Keshet E: A novel human-specific soluble vascular endothelial growth factor receptor 1: cell-type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circ Res 2008, 102:1566-1574.
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