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2009, Number 1

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Gac Med Mex 2009; 145 (1)

Linfangiogénesis en el cáncer y su papel en la diseminación metastásica

Utrera-Barillas MD, Castro-Manrreza ME, Gutiérrez-Rodríguez M, Benítez-Bribiesca L

Language: Spanish
References: 139
Page: 51-60
PDF size: 209.91 Kb.


ABSTRACT

It is well-known that there are different tumor-type-dependent metastatic patterns. For example, in carcinomas metastatic spread is preferentially via the lymphatic system by which they reach regional lymph nodes through pre-existent afferent lymph vessels and/or newly formed lymph capillaries; while in sarcomas the favored pathway is through blood vessels. These metastatic patterns have been used for many years by clinicians and surgeons for staging and tumor resection, particularly in the case of breast cancer. Recently this knowledge has been applied to detection and resection of sentinel lymph nodes. The lymphatic system drains the interstitial fluid from tissues and reincorporates it into the blood flow; in addition, it forms part of the host’s immune defense and in pathological conditions, induces different types of lymph edema and participates in tumor invasion and metastasis. Although, the study of lymphangiogenesis was stagnated for several decades, it was not until a few years ago that biomolecular mechanisms were discovered and many specific markers are now in use to study the process of tumor dissemination and metastasis. There is a tendency to utilize molecular knowledge in clinical settings for grading and estimating prognostic significance of tumors as well as to develop specific therapeutic strategies.


REFERENCES

  1. Alitalo K, Tammela T, Petrova TV. Lymphangiogenesis in development and human disease. Nature 2005;438:946-953.

  2. Pepper MS, Skobe M. Lymphatic endothelium: morphological, molecular and functional properties. J Cell Biol 2003;163:209-213.

  3. Schwartz GF, Giuliano AE, Veronesi U. Consensus Conference Committee.Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast. Cancer 2002;94:2542-2551.

  4. Ito M, Moriya T, Ishida T, Usami S, Kasajima A, Sasano H, et al. Significance of pathological evaluation for lymphatic vessel invasion in invasive breast cancer. Breast Cancer 2007;14:381-387.

  5. Brown P. Lymphatic system: Unlocking the drains. Nature 2005;436:456-458.

  6. Shayan R, Achen MG, Stacker SA. Lymphatic vessels in cancer metastasis: Bridging the gaps. Carcinogenesis 2006;27:1729-1738.

  7. Triolo Va. Nineteenth century foundations of cancer research advances in tumor pathology, nomenclature, and theories of oncogenesis. Cancer Res 1965;25:75-106.

  8. Halsted WS. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg 1894;20:497-555.

  9. Barcroft H. Review lecture. Bayliss-Starling Memorial Lecture 1976. Lymph formation by secretion or filtration? J Physiol 1976;260:1-20.

  10. Kaipainen A, Korhonen J, Mustonen T, van Hinsbergh VW, Fang GH,Dumont D, et al. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci USA 1995;92:3566-3570.

  11. Breiteneder-Geleff S, Soleiman A, Kowalski H, Horvat R, Amann G,Kriehuber E, et al. Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: Podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 1999;154:385-394.

  12. Petrova TV, Mäkinen T, Mäkelä TP, Saarela J, Virtanen I, Ferrell RE, et al.Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J 2002;21:4593-4599.

  13. Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, et al. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 1999;144:789-801.

  14. Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol 2002;15:434-440.

  15. Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, et al.Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 1997;276:1423-1425.

  16. Stacker SA, Achen MG, Jussila L, Baldwin ME, Alitalo K. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer 2002;2:573-583.

  17. Yuan L, Moyon D, Pardanaud L, Bréant C, Karkkainen MJ, Alitalo K, et al.Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 2002;129:4797-4806.

  18. Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis.Nat Rev Mol Cell Biol 2007;8:464-478.

  19. Karpanen T, Alitalo K. Molecular biology and pathology of lymphangiogenesis.Annu Rev Pathol 2008;3:367-397.

  20. Stacker SA, Farnsworth RH, Karnezis T, Shayan R, Smith DP, Paavonen K, et al. Molecular pathways for lymphangiogenesis and their role in human disease. Novartis Found Symp 2007;281:38-43.

  21. Benest AV, Harper SJ, Yla Herttuala S, Alitalo K, Bates DO. VEGF-C induced angiogenesis preferentially occurs at a distance from lymphangiogenesis. Cardiovasc Res 2008;78:315-323.

  22. Witte MH, Jones K, Wilting J, Dictor M, Selg M, McHale N, et al. Structure function relationships in the lymphatic system and implications for cancer biology. Cancer Metastasis Rev 2006;25:159-184.

  23. Oliver G. Lymphatic vasculature development. Nat Rev Immunol 2004;4:35-45.

  24. Hirakawa S, Hong YK, Harvey N, Schacht V, Matsuda K, Libermann T, et al. Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. Am J Pathol 2003;162:575-586.

  25. Podgrabinska S, Braun P, Velasco P, Kloos B, Pepper MS, Skobe M.Molecular characterization of lymphatic endothelial cells. Proc Natl Acad Sci USA 2002;99:16069-16074.

  26. Shibuya M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. J Biochem Mol Biol 2006;39:469-478.

  27. Roy H, Bhardwaj S, Ylä-Herttuala S. Biology of vascular endothelial growth factors. FEBS Lett 2006;580:2879-2887.

  28. McColl BK, Stacker SA, Achen MG. Molecular regulation of the VEGF familyinducers of angiogenesis and lymphangiogenesis. APMIS 2004;112:463-480.

  29. Goldman J, Rutkowski JM, Shields JD, Pasquier MC, Cui Y, Schmökel HG,et al. Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesis. FASEB J 2007;21:1003-1012.

  30. Wirzenius M, Tammela T, Uutela M, He Y, Odorisio T, Zambruno G, et al.Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med 2007;204:1431-1440.

  31. Dias S, Choy M, Alitalo K, Rafii S. Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. Blood 2002;99:2179-2184.

  32. Su JL, Yen CJ, Chen PS, Chuang SE, Hong CC, Kuo IH, et al. The role of the VEGF-C/VEGFR-3 axis in cancer progression. Br J Cancer 2007;96:541-545.

  33. Su JL, Yang PC, Shih JY, Yang CY, Wei LH, Hsieh CY, et al. The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells. Cancer Cell 2006 9:209-223.

  34. Mäkinen T, Veikkola T, Mustjoki S, Karpanen T, Catimel B, Nice EC, et al.Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J 2001;20:4762-4773.

  35. Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, et al.Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 2002;196:1497-1506.

  36. Ogawa E, Takenaka K, Yanagihara K, Kurozumi M, Manabe T, Wada H, et al. Clinical significance of VEGF-C status in tumour cells and stromal macrophages in non-small cell lung cancer patients. Br J Cancer 2004;91:498-503.

  37. Schoppmann SF, Fenzl A, Nagy K, Unger S, Bayer G, Geleff S, et al. VEGFC expressing tumor-associated macrophages in lymph node positive breast cancer: impact on lymphangiogenesis and survival. Surgery 2006;139:839-846.

  38. Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 2004;113:1040-1050.

  39. Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H, Tomita M, et al.Inflammation-induced lymphangiogenesis in the cornea arises from CD11bpositive macrophages. J Clin Invest 2005;115:2363-2372.

  40. Kerjaschki D. The crucial role of macrophages in lymphangiogenesis. J Clin Invest 2005;115:2316-2319.

  41. Baldwin ME, Halford MM, Roufail S, Williams RA, Hibbs ML, Grail D, et al.Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Mol Cell Biol 2005;25:2441-2449.

  42. Matsuo M, Yamada S, Koizumi K, Sakurai H, Saiki I. Tumour-derived fibroblast growth factor-2 exerts lymphangiogenic effects through Akt/mTOR/ p70S6kinase pathway in rat lymphatic endothelial cells. Eur J Cancer 2007;43:1748-1754.

  43. Cao Y. Direct role of PDGF-BB in lymphangiogenesis and lymphatic metastasis.Cell Cycle 2005;4:228-230.

  44. Cao R, Björndahl MA, Gallego MI, Chen S, Religa P, Hansen AJ, et al.Hepatocyte growth factor is a lymphangiogenic factor with an indirect mechanism of action. Blood 2006;107:3531-3536.

  45. Yang H, Li M, Chai H, Yan S, Zhang R, Yao Q, Chen C. Expression and regulation of neuropilins and VEGF receptors by TNF-alpha in human endothelial cells. J Surg Res 2004;122:249-255.

  46. Chen C, Li M, Chai H, Yang H, Fisher WE, Yao Q. Roles of neuropilins in neuronal development, angiogenesis, and cancers. World J Surg 2005;29:271- 275.

  47. Kärpänen T, Heckman CA, Keskitalo S, Jeltsch M, Ollila H, Neufeld G, et al. Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. FASEB J 2006;20:1462-1472.

  48. Vlahakis NE, Young BA, Atakilit A, Sheppard D. The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1. J Biol Chem 2005;280:4544-4552.

  49. Wang JF, Zhang XF, Groopman JE. Stimulation of beta 1 integrin induces tyrosine phosphorylation of vascular endothelial growth factor receptor-3 and modulates cell migration. J Biol Chem 2001;276:41950-1957.

  50. Petrova TV, Karpanen T, Norrmén C, Mellor R, Tamakoshi T, Finegold D,et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med 2004;10:974-981.

  51. Seo S, Fujita H, Nakano A, Kang M, Duarte A, Kume T. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol 2006;294:458-470.

  52. Saharinen P, Kerkelä K, Ekman N, Marron M, Brindle N, Lee GM, et al.Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. J Cell Biol 2005;169:239-243.

  53. Sebzda E, Hibbard C, Sweeney S, Abtahian F, Bezman N, Clemens G, et al.Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Dev Cell 2006;11:349-361.

  54. Kreuger J, Nilsson I, Kerjaschki D, Petrova T, Alitalo K, Claesson-Welsh L. Early lymph vessel development from embryonic stem cells. Arterioscler Thromb Vasc Biol 2006;26:1073-1078.

  55. Abtahian F, Guerriero A, Sebzda E, Lu MM, Zhou R, Mocsai A, et al.Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 2003;299:247-251.

  56. Mäkinen T, Adams RH, Bailey J, Lu Q, Ziemiecki A, Alitalo K, et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev 2005;19:397-410.

  57. Wong SY, Hynes RO. Tumor-lymphatic interactions in an activated stromal microenvironment. J Cell Biochem 2007;101:840-850.

  58. Longatto Filho A, Martins A, Costa SM, Schmitt FC. VEGFR-3 expression in breast cancer tissue is not restricted to lymphatic vessels. Pathol Res Pract 2005;201:93-99.

  59. Evangelou E, Kyzas PA, Trikalinos TA. Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach. Mod Pathol 2005;18:1490-1497.

  60. Johnson LA, Prevo R, Clasper S, Jackson DG. Inflammation-induced uptake and degradation of the lymphatic endothelial hyaluronan receptor LYVE-1. J Biol Chem 2007;282:33671-33680.

  61. Mouta-Carreira C, Nasser SM, di Tomaso E, Padera TP, Boucher Y,Tomarev SI, et al. LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res 2001;61:8079-8084.

  62. Yong C, Bridenbaugh EA, Zawieja DC, Swartz MA. Microarray analysis of VEGF-C responsive genes in human lymphatic endothelial cells. Lymphat Res Biol 2005;3:183-207.

  63. Garrafa E, Trainini L, Benetti A, Saba E, Fezzardi L, Lorusso B, et al.Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues. Lymphology 2005;38:159-166.

  64. Albertini JJ, Cruse CW, Rapaport D, Wells K, Ross M, DeConti R, et al.Intraoperative radio-lympho-scintigraphy improves sentinel lymph node identification for patients with melanoma. Ann Surg 1996;223:217-224.

  65. Cody HS , Borgen PI, Tan LK. Redefining prognosis in node-negative breast cancer: can sentinel lymph node biopsy raise the threshold for systemic adjuvant therapy? Ann Surg Oncol 2004;11:227S-230S.

  66. Mamounas EP, Brown A, Anderson S, Smith R, Julian T, Miller B, et al.Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2005;23:2694-2702.

  67. Barroso-Bravo S, Zarco-Espinosa G, Alvarado-Cabrero I, Valenzuela-Flores G, Pichardo-Romero P, Rodríguez-Cuevas S. Mapeo linfático y linfadenectomía del ganglio centinela para evitar la disección axilar en mujeres con cáncer temprano de mama. Cir Ciruj 2005;73:437-441.

  68. Takeuchi H, Kitajima M, Kitagawa Y. Sentinel lymph node as a target of molecular diagnosis of lymphatic micrometastasis and local immunoresponse to malignant cells. Cancer Sci 2008 Mar;99:441-450.

  69. Qian CN, Berghuis B, Tsarfaty G, Bruch M, Kort EJ, Ditlev J, et al. Preparing the “soil”: the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer Res 2006;66:10365-10376.

  70. Van den Eynden GG, Vandenberghe MK, van Dam PJ, Colpaert CG, van Dam P, Dirix LY, et al. Increased sentinel lymph node lymphangiogenesis is associated with nonsentinel axillary lymph node involvement in breast cancer patients with a positive sentinel node. Clin Cancer Res 2007;13:5391-5397.

  71. Hirakawa S, Brown LF, Kodama S, Paavonen K, Alitalo K, Detmar M. VEGFC-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood 2007;109:1010-1017.

  72. Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, et al.Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med 2001;7:192-198.

  73. Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 2001;20:672-682.

  74. Eichten A, Hyun WC, Coussens LM. Distinctive features of angiogenesis and lymphangiogenesis determine their functionality during de novo tumor development. Cancer Res 2007;67:5211-5220.

  75. Shields JD, Emmett MS, Dunn DB, Joory KD, Sage LM, Rigby H, et al.Chemokine-mediated migration of melanoma cells towards lymphatics¯ a mechanism contributing to metastasis. Oncogene 2007;26:2997-3005.

  76. Fukunaga S, Maeda K, Noda E, Inoue T, Wada K, Hirakawa K. Association between expression of vascular endothelial growth factor C, chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer. Oncology 2006;71:204-211.

  77. Mashino K, Sadanaga N, Yamaguchi H, Tanaka F, Ohta M, Shibuta K, et al.Expression of chemokine receptor CCR7 is associated with lymph node metastasis of gastric carcinoma. Cancer Res 2002;62:2937-2941.

  78. Takanami I. Overexpression of CCR7 mRNA in nonsmall cell lung cancer: correlation with lymph node metastasis. Int J Cancer 2003;105:186-189.

  79. Ji RC. Lymphatic endothelial cells, lymphangiogenesis, and extracellular matrix. Lymphat Res Biol 2006;4:83-100.

  80. Dua RS, Gui GP, Isacke CM. Endothelial adhesion molecules in breast cancer invasion into the vascular and lymphatic systems. Eur J Surg Oncol 2005;31:824-832.

  81. Lu Y, Yang Q, Du Y, Feng G, Yang C. Expression analysis of lymphangiogenic factors in human colorectal cancer with quantitative RT-PCR. Cancer Invest 2007;25:393-396.

  82. Bono P, Wasenius VM, Heikkilä P, Lundin J, Jackson DG, Joensuu H. High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer. Clin Cancer Res 2004;10:7144-149.

  83. Yu M, Tang Z, Alousi S, Berk RS, Miller F, Kosir MA. Expression patterns of lymphangiogenic and angiogenic factors in a model of breast ductal carcinoma in situ. Am J Surg 2007;194:594-599.

  84. van Iterson V, Leidenius M, von Smitten K, Bono P, Heikkilä P. VEGF-D in association with VEGFR-3 promotes nodal metastasis in human invasive lobular breast cancer. Am J Clin Pathol 2007;128:759-766.

  85. Saad RS, Kordunsky L, Liu YL, Denning KL, Kandil HA, Silverman JF.Lymphatic microvessel density as prognostic marker in colorectal cancer. Mod Pathol 2006;19:1317-1323.

  86. Duff SE, Jeziorska M, Kumar S, Haboubi N, Sherlock D, O’Dwyer ST, et al.Lymphatic vessel density, microvessel density and lymphangiogenic growth factor expression in colorectal cancer. Colorectal Dis 2007;9:793-800.

  87. Chen W, Shen W, Chen M, Cai G, Liu X. Study on the relationship between lymphatic vessel density and distal intramural spread of rectal cancer. Eur Surg Res 2007;39:332-339.

  88. Brakenhielm E, Burton JB, Johnson M, Chavarria N, Morizono K, Chen I,et al. Modulating metastasis by a lymphangiogenic switch in prostate cancer. Int J Cancer 2007;121:2153-2161.

  89. Zu X, Tang Z, Li Y, Gao N, Ding J, Qi L. Vascular endothelial growth factor-C expression in bladder transitional cell cancer and its relationship to lymph node metastasis. BJU Int 2006;98:1090-1093.

  90. Van Trappen PO, Steele D, Lowe DG, Baithun S, Beasley N, Thiele W, 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;201:544-554.

  91. Longatto-Filho A, Pinheiro C, Pereira SM, Etlinger D, Moreira MA, Jubà LF,et al. Lymphatic vessel density and epithelial D2-40 immunoreactivity in preinvasive and invasive lesions of the uterine cervix. Gynecol Oncol 2007;107:45-51.

  92. de la Torre NG, Buley I, Wass JA, Turner HE. Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: Relationship to type and tumour behaviour. Endocr Relat Cancer 2006;13:931-944.

  93. Yuan P, Temam S, El-Naggar A, Zhou X, Liu DD, Lee JJ, et al. Overexpression of podoplanin in oral cancer and its association with poor clinical outcome. Cancer 2006;107:563-569.

  94. Miyahara M, Tanuma J, Sugihara K, Semba I. Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters inoral squamous cell carcinoma. Cancer 2007;110:1287-1294.

  95. Nakamura Y, Yasuoka H, Tsujimoto M, Kurozumi K, Nakahara M, Nakao K,et al. Importance of lymph vessels in gastric cancer: A prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer. J Clin Pathol 2006;59:77-82.

  96. van der Schaft DW, Pauwels P, Hulsmans S, Zimmermann M, van de Poll-Franse LV, Griffioen AW. Absence of lymphangiogenesis in ductal breast cancer at the primary tumor site. Cancer Lett 2007;254:128-136.

  97. Schoppmann SF, Birner P, Studer P, Breiteneder-Geleff S. Lymphatic microvessel density and lymphovascular invasion assessed by anti-podoplanin immunostaining in human breast cancer. Anticancer Res 2001;21:2351-2355.

  98. Schoppmann SF, Birner P, Stöckl J, Kalt R, Ullrich R, Caucig C, et al.Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol 2002;161:947-956.

  99. Van Trappen PO, Steele D, Lowe DG, Baithun S, Beasley N, Thiele W, 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;201:544-554.

  100. Roma AA, Magi-Galluzzi C, Kral MA, Jin TT, Klein EA, Zhou M. Peritumoral lymphatic invasion is associated with regional lymph node metastases in prostate adenocarcinoma. Mod Pathol 2006;19(3):392-398.

  101. Zeng Y, Opeskin K, Horvath LG, Sutherland RL, Williams ED. Lymphatic vessel density and lymph node metastasis in prostate cancer. Prostate 2005;65:222-230.

  102. Stefansson IM, Salvesen HB, Akslen LA. Vascular proliferation is important for clinical progress of endometrial cancer. Cancer Res 2006;66:3303-3309.

  103. Dadras SS, Lange-Asschenfeldt B, Velasco P, Nguyen L, Vora A, Muzikansky A, et al. Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. Mod Pathol 2005;18:1232-1242.

  104. Padera TP, Kadambi A, di Tomaso E, Carreira CM, Brown EB, Boucher Y,et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 2002;296:1883-1886.

  105. Hall FT, Freeman JL, Asa SL, Jackson DG, Beasley NJ. Intratumoral lymphatics and lymph node metastases in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 2003;129:716-19.

  106. Audet N, Beasley NJ, MacMillan C, Jackson DG, Gullane PJ, Kamel-Reid S. Lymphatic vessel density, nodal metastases, and prognosis in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 2005;131:1065-1070.

  107. Maula SM, Luukkaa M, Grénman R, Jackson D, Jalkanen S, Ristamäki R.Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. Cancer Res 2003;63:1920-1926.

  108. Aishima S, Nishihara Y, Iguchi T, Taguchi K, Taketomi A, Maehara Y, et al.Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma. Mod Pathol 2008;21:256-264.

  109. Ishikawa Y, Aida S, Tamai S, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, et al. Significance of lymphatic invasion and proliferation on regional lymph node metastasis in renal cell carcinoma. Am J Clin Pathol 2007;128:198-207.

  110. Siriwardena BS, Kudo Y, Ogawa I, Udagama MN, Tilakaratne WM, Takata T. VEGF-C is associated with lymphatic status and invasion in oral cancer. J Clin Pathol 2008;61:103-108.

  111. Wong SY, Haack H, Crowley D, Barry M, Bronson RT, Hynes RO. Tumorsecreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis. Cancer Res 2005;65:9789-9798.

  112. Witte D, Thomas A, Ali N, Carlson N, Younes M. Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma. Anticancer Res 2002;22:1463-1466.

  113. Jüttner S, Wissmann C, Jöns T, Vieth M, Hertel J, Gretschel S, et al.Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma. J Clin Oncol 2006;24:228-240.

  114. Jennbacken K, Vallbo C, Wang W, Damber JE. Expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis. Prostate 2005;65:110-116.

  115. Saintigny P, Kambouchner M, Ly M, Gomes N, Sainte-Catherine O, Vassy R, et al. Vascular endothelial growth factor-C and its receptor VEGFR-3 in nonsmall- cell lung cancer: concurrent expression in cancer cells from primary tumour and metastatic lymph node. Lung Cancer 2007;58:205-213.

  116. Denardo DG, Johansson M, Coussens LM. Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev 2008;27:11-18.

  117. Prendergast GC, Jaffee EM. Cancer immunologists and cancer biologists: Why we didn’t talk then but need to now. Cancer Res 2007;67:3500-3504.

  118. Kaneko I, Tanaka S, Oka S, Kawamura T, Hiyama T, Ito M, et al. Lymphatic vessel density at the site of deepest penetration as a predictor of lymph node metastasis in submucosal colorectal cancer. Dis Colon Rectum 2007;50:13-21.

  119. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006;124:263-266.

  120. Zhang XH, Huang DP, Guo GL, Chen GR, Zhang HX, Wan L, et al.Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer. BMC Cancer 2008;8:4.

  121. Da MX, Wu XT, Wang J, Guo TK, Zhao ZG, Luo T, et al. Expression of cyclooxygenase-2 and vascular endothelial growth factor-C correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer. Arch Med Res 2008;39:92-99.

  122. Iwata C, Kano MR, Komuro A, Oka M, Kiyono K, Johansson E, et al.Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via reduction of lymphangiogenesis. Cancer Res 2007;67:10181-10189.

  123. Koizumi K, Kozawa Y, Ohashi Y, Nakamura ES, Aozuka Y, Sakurai H, et al.CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro. Oncol Rep 2007;17:1511-1516.

  124. Wong SY, Hynes RO. Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle 2006;5:812-817.

  125. Kaifi JT, Yekebas EF, Schurr P, Obonyo D, Wachowiak R, Busch P, et al.Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. J Natl Cancer Inst 2005 Dec;97:1840-1847.

  126. Schimanski CC, Schwald S, Simiantonaki N, Jayasinghe C, Gönner U,Wilsberg V, et al. Effect of chemokine receptors CXCR4 and CCR7 on the metastatic behavior of human colorectal cancer. Clin Cancer Res 2005;11:1743-1750.

  127. Schimanski CC, Bahre R, Gockel I, Müller A, Frerichs K, Hörner V, et al.Dissemination of hepatocellular carcinoma is mediated via chemokine receptor CXCR4. Br J Cancer 2006;95:210-217.

  128. Sleeman JP. The lymph node as a bridgehead in the metastatic dissemination of tumors. Recent Results Cancer Res 2000;157:55-81.

  129. He Y, Kozaki K, Karpanen T, Koshikawa K, Yla-Herttuala S, Takahashi T,et al. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst 2002;94:819-825.

  130. Zehnder-Fjallman AH, Marty C, Halin C, Hohn A, Schibli R, Ballmer-Hofer K, et al. Evaluation of anti-VEGFR-3 specific scFv antibodies as potential therapeutic and diagnostic tools for tumor lymph-angiogenesis. Oncol Rep 2007;18:933-941.

  131. Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, et al.Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 2007;131:463-475.

  132. Sundlisaeter E, Dicko A, Sakariassen P, Sondenaa K, Enger P, Bjerkvig R.Lymphangiogenesis in colorectal cancer¯ prognostic and therapeutic aspects. Int J Cancer 2007;121:1401-1409.

  133. Brideau G, Mäkinen MJ, Elamaa H, Tu H, Nilsson G, Alitalo K, et al.Endostatin overexpression inhibits lymphangiogenesis and lymph node metastasis in mice. Cancer Res 2007;67:11528-11535.

  134. Sun P, Gao J, Liu YL, Wei LW, Wu LP, Liu ZY. RNA interference (RNAi)-mediated vascular endothelial growth factor-C (VEGF-C) reduction interferes with lymphangiogenesis and enhances Epirubicin sensitivity of breast cancer cells. Mol Cell Biochem 2008;308:161-168.

  135. He XW, Liu T, Chen YX, Cheng DJ, Li XR, Xiao Y, et al. Calcium carbonate nanoparticle delivering vascular endothelial growth factor-C siRNA effectively inhibits lymphangiogenesis and growth of gastric cancer in vivo. Cancer Gene Ther 2008;15:193-202.

  136. Schoppmann SF, Horvat R, Birner P. Lymphatic vessels and lymphangiogenesis in female cancer: mechanisms, clinical impact and possible implications for anti-lymphangiogenic therapies. Oncol Rep 2002;9:455-460.

  137. Detmar M. Tumor angiogenesis. J Invest Dermatol Symp Proc 2000;5:20-23.

  138. Boucher Y, Baxter LT, Jain RK. Interstitial pressure gradients in tissueisolated and subcutaneous tumors: implications for therapy. Cancer Res 1990;50:4478-4484.

  139. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-257.




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