The dual role of tumor lymphatic vessels in dissemination of metastases and immune response development

OncoImmunology

Volumn 5, Issue 7, 2016, Pages

  Stachura, Joanna ^a   Wachowska, Malgorzata ^a   Kilarski, Witold W ^b   Güç, Esra ^c   Golab, Jakub ^a   Muchowicz, Angelika ^a  

^a MEDICAL UNIVERSITY OF WARSAW   (Poland)

^b UNIVERSITY OF CHICAGO   (United States)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Anti lymphatic therapies; CCR7; lymphatic endothelial cells; photodynamic therapy; vascular endothelial growth factor

Indexed keywords

ANTINEOPLASTIC AGENT; AXITINIB; BEVACIZUMAB; CARBOPLATIN; CD99 ANTIGEN; CHEMOKINE RECEPTOR CCR7; CVX 060; IMC 3C5; INTERLEUKIN 6; LENALIDOMIDE; MEDI 3617; PACLITAXEL; PAZOPANIB; REGORAFENIB; SECONDARY LYMPHOID TISSUE CHEMOKINE; SORAFENIB; SUNITINIB; TREBANANIB; UNCLASSIFIED DRUG; VASCULOTROPIN C; VASCULOTROPIN D; VASCULOTROPIN E; VGX 100;

ANTIGEN PRESENTING CELL; CHEMICAL PHENOMENA; DENDRITIC CELL; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; GENE OVEREXPRESSION; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; KIDNEY CARCINOMA; LYMPH VESSEL; LYMPHANGIOGENESIS; METASTASIS; MULTIPLE CYCLE TREATMENT; NONHUMAN; PHOTODYNAMICS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECEPTOR DOWN REGULATION; REVIEW; SOLID TUMOR; TUMOR GROWTH;

EID: 84976542681     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2016.1182278     Document Type: Review

References (80)

1. S.A.Stacker, S.P.Williams, T.Karnezis, R.Shayan, S.B.Fox, M.G.Achen. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer 2014; 14:159-72; PMID:24561443; http://dx.doi.org/10.1038/nrc3677
2. M.Francois, A.Caprini, B.Hosking, F.Orsenigo, D.Wilhelm, C.Browne, K.Paavonen, T.Karnezis, R.Shayan, M.Downes et al. Sox18 induces development of the lymphatic vasculature in mice. Nature 2008; 456:643-7; PMID:18931657; http://dx.doi.org/10.1038/nature07391
3. A.W.Lund, F.V.Duraes, S.Hirosue, V.R.Raghavan, C.Nembrini, S.N.Thomas, A.Issa, S.Hugues, M.A.Swartz. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep 2012; 1:191-9; PMID:22832193; http://dx.doi.org/10.1016/j.celrep.2012.01.005
4. H.Maby-El Hajjami, T.V.Petrova. Developmental and pathological lymphangiogenesis:from models to human disease. Histochem Cell Biol 2008; 130:1063-78; PMID:18946678; http://dx.doi.org/10.1007/s00418-008-0525-5
5. A.Louveau, I.Smirnov, T.J.Keyes, J.D.Eccles, S.J.Rouhani, J.D.Peske, N.C.Derecki, D.Castle, J.W.Mandell, K.S.Lee et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015; 523:337-41; PMID:26030524; http://dx.doi.org/10.1038/nature14432
6. P.Baluk, J.Fuxe, H.Hashizume, T.Romano, E.Lashnits, S.Butz, D.Vestweber, M.Corada, C.Molendini, E.Dejana et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med 2007; 204:2349-62; PMID:17846148; http://dx.doi.org/10.1084/jem.20062596
7. L.C.Dieterich, M.Detmar. Tumor lymphangiogenesis and new drug development. Adv Drug Deliv Rev 2016 Apr 1; 99(Pt B):148-60; PMID:26705849; http://dx.doi.org/10.1016/j.addr.2015.12.011
8. S.Hirosue, E.Vokali, V.R.Raghavan, M.Rincon-Restrepo, A.W.Lund, P.Corthesy-Henrioud, F.Capotosti, C.Halin Winter, S.Hugues, M.A.Swartz. Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming:a new role for lymphatic endothelial cells. J Immunol 2014; 192:5002-11; PMID:24795456; http://dx.doi.org/10.4049/jimmunol.1302492
9. A.W.Lund, M.A.Swartz. Role of lymphatic vessels in tumor immunity:passive conduits or active participants? J Mammary Gland Biol Neoplasia 2010; 15:341-52; PMID:20835756; http://dx.doi.org/10.1007/s10911-010-9193-x
10. A.L.Fletcher, D.Malhotra, S.J.Turley. Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol 2011; 32:12-8; PMID:21147035; http://dx.doi.org/10.1016/j.it.2010.11.002
11. E.Rovenska, J.Rovensky. Lymphatic vessels:structure and function. Isr Med Assoc J 2011; 13:762-8; PMID:22332449
12. A.G.Warren, H.Brorson, L.J.Borud, S.A.Slavin. Lymphedema:a comprehensive review. Ann Plast Surg 2007; 59:464-72; PMID:17901744; http://dx.doi.org/10.1097/01.sap.0000257149.42922.7e
13. B.Vigl, D.Aebischer, M.Nitschke, M.Iolyeva, T.Rothlin, O.Antsiferova, C.Halin. Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner. Blood 2011; 118:205-15; PMID:21596851; http://dx.doi.org/10.1182/blood-2010-12-326447
14. T.Duong, P.Koopman, M.Francois. Tumor lymphangiogenesis as a potential therapeutic target. J Oncol 2012; 2012:204946; PMID:22481918; http://dx.doi.org/10.1155/2012/204946
15. S.F.Schoppmann, P.Birner, J.Stockl, R.Kalt, R.Ullrich, C.Caucig, E.Kriehuber, K.Nagy, K.Alitalo, D.Kerjaschki. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol 2002; 161:947-56; PMID:12213723; http://dx.doi.org/10.1016/S0002-9440(10)64255-1
16. M.G.Achen, B.K.McColl, S.A.Stacker. Focus on lymphangiogenesis in tumor metastasis. Cancer Cell 2005; 7:121-7; PMID:15710325; http://dx.doi.org/10.1016/j.ccr.2005.01.017
17. Y.Min, S.Ghose, K.Boelte, J.Li, L.Yang, P.C.Lin. C/EBP-delta regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1alpha. Oncogene 2011; 30:4901-9; PMID:21666710; http://dx.doi.org/10.1038/onc.2011.187
18. L.Schito, S.Rey, M.Tafani, H.Zhang, C.C.Wong, A.Russo, M.A.Russo, G.L.Semenza. Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. Proc Natl Acad Sci USA 2012; 109:E2707-16; PMID:23012449; http://dx.doi.org/10.1073/pnas.1214019109
19. J.P.Bridges, S.Lin, M.Ikegami, J.M.Shannon. Conditional hypoxia inducible factor-1alpha induction in embryonic pulmonary epithelium impairs maturation and augments lymphangiogenesis. Dev Biol 2012; 362:24-41; PMID:22094019; http://dx.doi.org/10.1016/j.ydbio.2011.10.033
20. F.Morfoisse, A.Kuchnio, C.Frainay, A.Gomez-Brouchet, M.B.Delisle, S.Marzi, A.C.Helfer, F.Hantelys, F.Pujol, J.Guillermet-Guibert et al. Hypoxia induces VEGF-C expression in metastatic tumor cells via a HIF-1alpha-independent translation-mediated mechanism. Cell reports 2014; 6:155-67; PMID:24388748; http://dx.doi.org/10.1016/j.celrep.2013.12.011
21. E.K.Rofstad, K.Galappathi, B.S.Mathiesen. Tumor interstitial fluid pressure – a link between tumor hypoxia, microvascular density, and lymph node metastasis. Neoplasia 2014; 16:586-94; PMID:25117980; http://dx.doi.org/10.1016/j.neo.2014.07.003
22. P.O.Van Trappen, D.Steele, D.G.Lowe, S.Baithun, N.Beasley, W.Thiele, H.Weich, J.Krishnan, J.H.Shepherd, M.S.Pepper et al. Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D, and their receptor VEGFR-3, during different stages of cervical carcinogenesis. J Pathol 2003; 201:544-54; PMID:14648657; http://dx.doi.org/10.1002/path.1467
23. H.Ji, R.Cao, Y.Yang, Y.Zhang, H.Iwamoto, S.Lim, M.Nakamura, P.Andersson, J.Wang, Y.Sun et al. TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling. Nat Commun 2014; 5:4944; PMID:25229256; http://dx.doi.org/10.1038/ncomms5944
24. Y.S.Maeng, B.Aguilar, S.I.Choi, E.K.Kim. Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis. Oncogene 2016; 35:196-205; PMID:25772247; http://dx.doi.org/10.1038/onc.2015.73
25. Y.S.Maeng, R.Lee, B.Lee, S.I.Choi, E.K.Kim. Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells. Scientific Rep 2016; 6:20739; PMID:26857144; http://dx.doi.org/10.1038/srep20739
26. P.S.Steeg. Cancer biology:emissaries set up new sites. Nature 2005; 438:750-1; PMID:16341000; http://dx.doi.org/10.1038/438750b
27. E.Lee, N.B.Pandey, A.S.Popel. Pre-treatment of mice with tumor-conditioned media accelerates metastasis to lymph nodes and lungs:a new spontaneous breast cancer metastasis model. Clin Exp Metastasis 2014; 31:67-79; PMID:23963763; http://dx.doi.org/10.1007/s10585-013-9610-9
28. J.Xu, C.Zhang, Y.He, H.Wu, Z.Wang, W.Song, W.Li, W.He, S.Cai, W.Zhan. Lymphatic endothelial cell-secreted CXCL1 stimulates lymphangiogenesis and metastasis of gastric cancer. Int J Cancer J Int du Cancer 2012; 130:787-97; PMID:21387301; http://dx.doi.org/10.1002/ijc.26035
29. E.Lee, E.J.Fertig, K.Jin, S.Sukumar, N.B.Pandey, A.S.Popel. Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis. Nat Commun 2014; 5:4715; PMID:25178650; http://dx.doi.org/10.1038/ncomms5715
30. Z.T.Schafer, J.S.Brugge. IL-6 involvement in epithelial cancers. J Clin Investig 2007; 117:3660-3; PMID:18060028; http://dx.doi.org/10.1172/JCI34237
31. Q.Chang, E.Bournazou, P.Sansone, M.Berishaj, S.P.Gao, L.Daly, J.Wels, T.Theilen, S.Granitto, X.Zhang et al. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia 2013; 15:848-62; PMID:23814496; http://dx.doi.org/10.1593/neo.13706
32. E.J.Fertig, E.Lee, N.B.Pandey, A.S.Popel. Analysis of gene expression of secreted factors associated with breast cancer metastases in breast cancer subtypes. Scientific reports 2015; 5:12133; PMID:26173622; http://dx.doi.org/10.1038/srep12133
33. K.Oh, O.Y.Lee, S.Y.Shon, O.Nam, P.M.Ryu, M.W.Seo, D.S.Lee. A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model. Breast Cancer Res 2013; 15:R79; PMID:24021059; http://dx.doi.org/10.1186/bcr3473
34. T.Amioka, Y.Kitadai, S.Tanaka, K.Haruma, M.Yoshihara, W.Yasui, K.Chayama. Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa. Eur J Cancer 2002; 38:1413-9; PMID:12091074; http://dx.doi.org/10.1016/S0959-8049(02)00106-5
35. J.D.Shields, M.S.Emmett, D.B.Dunn, K.D.Joory, L.M.Sage, H.Rigby, P.S.Mortimer, A.Orlando, J.R.Levick, D.O.Bates. Chemokine-mediated migration of melanoma cells towards lymphatics–a mechanism contributing to metastasis. Oncogene 2007; 26:2997-3005; PMID:17130836; http://dx.doi.org/10.1038/sj.onc.1210114
36. M.R.Pan, M.F.Hou, H.C.Chang, W.C.Hung. Cyclooxygenase-2 up-regulates CCR7 via EP2/EP4 receptor signaling pathways to enhance lymphatic invasion of breast cancer cells. J Biol Chem 2008; 283:11155-63; PMID:18319253; http://dx.doi.org/10.1074/jbc.M710038200
37. C.Denkert, K.J.Winzer, B.M.Muller, W.Weichert, S.Pest, M.Kobel, G.Kristiansen, A.Reles, A.Siegert, H.Guski et al. Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer 2003; 97:2978-87; PMID:12784332; http://dx.doi.org/10.1002/cncr.11437
38. E.Tutunea-Fatan, M.Majumder, X.Xin, P.K.Lala. The role of CCL21/CCR7 chemokine axis in breast cancer-induced lymphangiogenesis. Mol Cancer 2015; 14:35; PMID:25744065; http://dx.doi.org/10.1186/s12943-015-0306-4
39. J.D.Shields, M.E.Fleury, C.Yong, A.A.Tomei, G.J.Randolph, M.A.Swartz. Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling. Cancer Cell 2007; 11:526-38; PMID:17560334; http://dx.doi.org/10.1016/j.ccr.2007.04.020
40. C.S.McKimmie, M.D.Singh, K.Hewit, O.Lopez-Franco, M.Le Brocq, S.Rose-John, K.M.Lee, A.H.Baker, R.Wheat, D.J.Blackbourn et al. An analysis of the function and expression of D6 on lymphatic endothelial cells. Blood 2013; 121:3768-77; PMID:23479571; http://dx.doi.org/10.1182/blood-2012-04-425314
41. F.Y.Wu, Z.L.Ou, L.Y.Feng, J.M.Luo, L.P.Wang, Z.Z.Shen, Z.M.Shao. Chemokine decoy receptor d6 plays a negative role in human breast cancer. Mol Cancer Res 2008; 6:1276-88; PMID:18708360; http://dx.doi.org/10.1158/1541-7786.MCR-07-2108
42. A.Muller, B.Homey, H.Soto, N.Ge, D.Catron, M.E.Buchanan, T.McClanahan, E.Murphy, W.Yuan, S.N.Wagner et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001; 410:50-6; PMID:11242036; http://dx.doi.org/10.1038/35065016
43. L.A.Johnson, S.Clasper, A.P.Holt, P.F.Lalor, D.Baban, D.G.Jackson. An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium. J Exp Med 2006; 203:2763-77; PMID:17116732; http://dx.doi.org/10.1084/jem.20051759
44. J.Yan, Y.Jiang, M.Ye, W.Liu, L.Feng. The clinical value of lymphatic vessel density, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 expression in patients with oral tongue squamous cell carcinoma. J Cancer Res Therapeutics 2014; 10 Suppl:C125-30; PMID:25450269; http://dx.doi.org/10.4103/0973-1482.145827
45. R.C.Winger, C.T.Harp, M.Y.Chiang, D.P.Sullivan, R.L.Watson, E.W.Weber, J.R.Podojil, S.D.Miller, W.A.Muller. Cutting edge:CD99 is a novel therapeutic target for control of T cell-mediated central nervous system autoimmune disease. J Immunol 2016; 196:1443-8; PMID:26773145; http://dx.doi.org/10.4049/jimmunol.1501634
46. O.Lou, P.Alcaide, F.W.Luscinskas, W.A.Muller. CD99 is a key mediator of the transendothelial migration of neutrophils. J Immunol 2007; 178:1136-43; PMID:17202377; http://dx.doi.org/10.4049/jimmunol.178.2.1136
47. K.Scotlandi, M.Zuntini, M.C.Manara, M.Sciandra, A.Rocchi, S.Benini, G.Nicoletti, G.Bernard, P.Nanni, P.L.Lollini et al. CD99 isoforms dictate opposite functions in tumour malignancy and metastases by activating or repressing c-Src kinase activity. Oncogene 2007; 26:6604-18; PMID:17471235; http://dx.doi.org/10.1038/sj.onc.1210481
48. A.R.Hajrasouliha, T.Funaki, Z.Sadrai, T.Hattori, S.K.Chauhan, R.Dana. Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis. Investig Ophthalmol Visual Sci 2012; 53:1244-50; PMID:22281820; http://dx.doi.org/10.1167/iovs.11-8668
49. A.C.Mita, C.H.Takimoto, M.Mita, A.Tolcher, K.Sankhala, J.Sarantopoulos, M.Valdivieso, L.Wood, E.Rasmussen, Y.N.Sun et al. Phase 1 study of AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, in combination with chemotherapy in adults with advanced solid tumors. Clin Cancer Res 2010; 16:3044-56; PMID:20501621; http://dx.doi.org/10.1158/1078-0432.CCR-09-3368
50. V.Dieras, H.Wildiers, J.Jassem, L.Y.Dirix, J.P.Guastalla, P.Bono, S.A.Hurvitz, A.Gonçalves, G.Romieu, S.A.Limentani et al. Trebananib (AMG 386) plus weekly paclitaxel with or without bevacizumab as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer:a phase 2 randomized study. Breast 2015; 24:182-90; PMID:25747197; http://dx.doi.org/10.1016/j.breast.2014.11.003
51. J.L.Spratlin, R.B.Cohen, M.Eadens, L.Gore, D.R.Camidge, S.Diab, S.Leong, C.O'Bryant, L.Q.Chow, N.J.Serkova et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 2010; 28:780-7; PMID:20048182; http://dx.doi.org/10.1200/JCO.2009.23.7537
52. K.Song, B.H.Herzog, M.Sheng, J.Fu, J.M.McDaniel, H.Chen, J.Ruan, L.Xia. Lenalidomide inhibits lymphangiogenesis in preclinical models of mantle cell lymphoma. Cancer Res 2013; 73:7254-64; PMID:24158094; http://dx.doi.org/10.1158/0008-5472.CAN-13-0750
53. E.Lee, S.J.Lee, J.E.Koskimaki, Z.Han, N.B.Pandey, A.S.Popel. Inhibition of breast cancer growth and metastasis by a biomimetic peptide. Scientific Rep 2014; 4:7139; PMID:25409905; http://dx.doi.org/10.1038/srep07139
54. S.M.Wilhelm, L.Adnane, P.Newell, A.Villanueva, J.M.Llovet, M.Lynch. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 2008; 7:3129-40; PMID:18852116; http://dx.doi.org/10.1158/1535-7163.MCT-08-0013
55. Z.Mihaly, Z.Sztupinszki, P.Surowiak, B.Gyorffy. A comprehensive overview of targeted therapy in metastatic renal cell carcinoma. Current cancer drug targets 2012; 12:857-72; PMID:22515521; http://dx.doi.org/10.2174/156800912802429265
56. M.Wachowska, A.Muchowicz, J.Golab. Targeting epigenetic processes in photodynamic therapy-induced anticancer immunity. Front Oncol 2015; 5:176; PMID:26284197; http://dx.doi.org/10.3389/fonc.2015.00176
57. P.Agostinis, K.Berg, K.A.Cengel, T.H.Foster, A.W.Girotti, S.O.Gollnick, S.M.Hahn, M.R.Hamblin, A.Juzeniene, D.Kessel et al. Photodynamic therapy of cancer:an update. CA Cancer J Clin 2011; 61:250-81; PMID:21617154; http://dx.doi.org/10.1017/S0009840X10002799
58. C.Norrmen, T.Tammela, T.V.Petrova, K.Alitalo. Biological basis of therapeutic lymphangiogenesis. Circulation 2011; 123:1335-51; PMID:21444892; http://dx.doi.org/10.1161/CIRCULATIONAHA.107.704098
59. W.W.Kilarski, A.Muchowicz, M.Wachowska, R.Mezyk-Kopec, J.Golab, M.A.Swartz, P.Nowak-Sliwinska. Optimization and regeneration kinetics of lymphatic-specific photodynamic therapy in the mouse dermis. Angiogenesis 2014; 17:347-57; PMID:23892627; http://dx.doi.org/10.1007/s10456-013-9365-6
60. M.Wachowska, A.Osiak, A.Muchowicz, M.Gabrysiak, A.Domagala, W.W.Kilarski, J.Golab. Investigation of cell death mechanisms in human lymphatic endothelial cells undergoing photodynamic therapy. Photodiagnosis and photodynamic therapy 2016; Jun;14:57-65; PMID:26868051; http://dx.doi.org/10.1016/j.pdpdt.2016.02.004.
61. K.Van der Jeught, L.Bialkowski, L.Daszkiewicz, K.Broos, C.Goyvaerts, D.Renmans, S.Van Lint, C.Heirman, K.Thielemans, K.Breckpot. Targeting the tumor microenvironment to enhance antitumor immune responses. Oncotarget 2015; 6:1359-81; PMID:25682197; http://dx.doi.org/10.18632/oncotarget.3204
62. R.Forster, A.Schubel, D.Breitfeld, E.Kremmer, I.Renner-Muller, E.WolfM.Lipp. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 1999; 99:23-33; PMID:10520991; http://dx.doi.org/10.1016/S0092-8674(00)80059-8
63. D.Raman, P.J.Baugher, Y.M.Thu, A.Richmond. Role of chemokines in tumor growth. Cancer Lett 2007; 256:137-65; PMID:17629396; http://dx.doi.org/10.1016/j.canlet.2007.05.013
64. J.Y.Li, Z.L.Ou, S.J.Yu, X.L.Gu, C.Yang, A.X.Chen, G.H.Di, Z.Z.Shen, Z.M.Shao. The chemokine receptor CCR4 promotes tumor growth and lung metastasis in breast cancer. Breast Cancer Res Treat 2012; 131:837-48; PMID:21479551; http://dx.doi.org/10.1007/s10549-011-1502-6
65. J.P.Johnson. Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. Cancer Metastasis Rev 1991; 10:11-22; PMID:1680575; http://dx.doi.org/10.1007/BF00046840
66. C.Rosette, R.B.Roth, P.Oeth, A.Braun, S.Kammerer, J.Ekblom, M.F.Denissenko. Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis 2005; 26:943-50; PMID:15774488; http://dx.doi.org/10.1093/carcin/bgi070
67. M.D.Diaz-Munoz, I.C.Osma-Garcia, M.A.Iniguez, M.Fresno. Cyclooxygenase-2 deficiency in macrophages leads to defective p110gamma PI3K signaling and impairs cell adhesion and migration. J Immunol 2013; 191:395-406; PMID:23733875; http://dx.doi.org/10.4049/jimmunol.1202002
68. W.T.Godbey, A.Atala. Directed apoptosis in Cox-2-overexpressing cancer cells through expression-targeted gene delivery. Gene Ther 2003; 10:1519-27; PMID:12900768; http://dx.doi.org/10.1038/sj.gt.3302012
69. M.Kanamori, K.Suzuki, T.Yasuda, T.Hori. CD99-positive soft tissue sarcoma with chromosomal translocation between 1 and 16 and inversion of chromosome 5. Oncology Lett 2012; 3:1213-5; PMID:22783420; http://dx.doi.org/10.3892/ol.2012.641
70. K.Takahashi, H.Mizukami, Y.Saga, Y.Takei, M.Urabe, A.Kume, S.Machida, H.Fujiwara, M.Suzuki, K.Ozawa. Suppression of lymph node and lung metastases of endometrial cancer by muscle-mediated expression of soluble vascular endothelial growth factor receptor-3. Cancer Sci 2013; 104:1107-11; PMID:23614535; http://dx.doi.org/10.1111/cas.12184
71. J.Hwang-Bo, K.H.Yoo, J.H.Park, H.S.Jeong, I.S.Chung. Recombinant canstatin inhibits angiopoietin-1-induced angiogenesis and lymphangiogenesis. Int J Cancer J Int du Cancer 2012; 131:298-309; PMID:21823121; http://dx.doi.org/10.1002/ijc.26353
72. K.Y.Han, D.T.Azar, A.Sabri, H.Lee, S.Jain, B.S.LeeJ.H.Chang. Characterization of the interaction between endostatin short peptide and VEGF receptor 3. Protein and peptide letters 2012; 19:969-74; PMID:22512651; http://dx.doi.org/10.2174/092986612802084465
73. V.Kinet, K.Castermans, S.Herkenne, C.Maillard, S.Blacher, M.Lion, A.Noël, J.A.Martial, I.Struman. The angiostatic protein 16K human prolactin significantly prevents tumor-induced lymphangiogenesis by affecting lymphatic endothelial cells. Endocrinology 2011; 152:4062-71; PMID:21862622; http://dx.doi.org/10.1210/en.2011-1081
74. N.Espagnolle, P.Barron, M.Mandron, I.Blanc, J.Bonnin, M.Agnel, E.Kerbelec, J.P.Herault, P.Savi, F.Bono et al. Specific inhibition of the VEGFR-3 tyrosine kinase by SAR131675 reduces peripheral and tumor associated immunosuppressive myeloid cells. Cancers 2014; 6:472-90; PMID:24589997; http://dx.doi.org/10.3390/cancers6010472
75. K.Kashima, M.Watanabe, Y.Satoh, J.Hata, N.Ishii, Y.Aoki. Inhibition of lymphatic metastasis in neuroblastoma by a novel neutralizing antibody to vascular endothelial growth factor-D. Cancer Sci 2012; 103:2144-52; PMID:22937829; http://dx.doi.org/10.1111/cas.12010
76. Y.Mumblat, O.Kessler, N.Ilan, G.Neufeld. Full-length Semaphorin-3C is an inhibitor of tumor lymphangiogenesis and metastasis. Cancer Res 2015; 75:2177-86; PMID:25808871; http://dx.doi.org/10.1158/0008-5472.CAN-14-2464
77. V.Patel, C.A.Marsh, R.T.Dorsam, C.M.Mikelis, A.Masedunskas, P.Amornphimoltham, C.A.Nathan, B.Singh, R.Weigert, A.A.Molinolo et al. Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer. Cancer Res 2011; 71:7103-12; PMID:21975930; http://dx.doi.org/10.1158/0008-5472.CAN-10-3192
78. X.P.Li, W.Jing, J.J.Sun, Z.Y.Liu, J.T.Zhang, W.Sun, W.Zhu, Y.Z.Fan. A potential small-molecule synthetic antilymphangiogenic agent norcantharidin inhibits tumor growth and lymphangiogenesis of human colonic adenocarcinomas through blocking VEGF-A,-C,-D/VEGFR-2,-3 “multi-points priming” mechanisms in vitro and in vivo. BMC Cancer 2015; 15:527; PMID:26187792; http://dx.doi.org/10.1186/s12885-015-1521-5
79. Y.Kodera, Y.Katanasaka, Y.Kitamura, H.Tsuda, K.Nishio, T.Tamura, F.Koizumi. Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3. Breast Cancer Res 2011; 13:R66; PMID:21693010; http://dx.doi.org/10.1186/bcr2903
80. R.Schmieder, J.Hoffmann, M.Becker, A.Bhargava, T.Muller, N.Kahmann, P.Ellinghaus, R.Adams, A.Rosenthal, K.H.Thierauch et al. Regorafenib (BAY 73-4506):antitumor and antimetastatic activities in preclinical models of colorectal cancer. Int J Cancer J Int du Cancer 2014; 135:1487-96; PMID:24347491; http://dx.doi.org/10.1002/ijc.28669