Abstract
In recent years, several functional molecules specifically expressed and localized in lymphatic endothelial cells, such as 5’-nucleotidase, lymphatic vessel endothelial receptor-1, vascular endothelial growth factor receptor-3, podoplanin and Prox-1, have been identified. The discovery of the lymphatic endothelial cell markers facilitated detailed analysis of the nature and structural organization of the lymphatic vessels and their growth (lymphangiogenesis). As a result, over the past few years, advances have been made in understanding the cellular and molecular aspects of physiological lymphangiogenesis and tumor-induced lymphangiogenesis. The biology of lymphangiogenesis, particularly the mechanism of its regulation, is very important in understanding the formation of the lymphatic system as a biological regulation system transporting tissue fluid and wandering cells, including lymphocytes, and disease involving lymphangiogenesis. The understanding of the molecular mechanism of lymphangiogenesis and the elucidation of the development of normal and pathological tissues are expected to lead to the development of therapy for intractable diseases, such as malignant tumors and lymphedema.
Similar content being viewed by others
References
Abtahian F, Guerriero A, Kahn MLet al. (2003) Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk.Science 299, 247–51.
Akagi K, Ikeda Y, Miyazaki Met al. (2000) Vascular endothelial growth factor-c (VEGF-C) expression in human colorectal cancer tissues.Br J Cancer 83, 887–91.
Alitalo K (2002) Growth factors controlling angiogenesis and lymph angiogenesis.Ugeskr Laeger 164, 3170–2.
Al-Rawi MA, Watkins G, Mansel RE, Jiang WG (2005) Interleukin 7 upregulates vascular endothelial growth factor D in breast cancer cells and induces lymphangiogenesisin vivo.Br J Surg 92, 305–10.
Arinaga M, Noguchi T, Takeno Set al. (2003) Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor-3 in patients with nonsmall cell lung carcinoma.Cancer 97, 457–64.
Auvinen MI, Sihvo EI, Ruohtula Tet al. (2002) Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma.J Clin Oncol 20, 2971–9.
Banerji S, Ni J, Wang S-Xet al. (1999) LYVE-1, a new homologue of the CD44 glycoprotein, Is a lymph-specific receptor for hyaluronan.J Cell Biol 144, 789–801.
Beasley NJ, Prevo R, Banerji S {eaet al.} (2002) Intratumoral lymphangiogenesis and lymph node metastasis in ehad and neck cancer.Cancer Res 62, 1315–20.
Bilchik A, Giuliano A, Essner Ret al. (1998) Universal application of intraoperative lymphatic mapping and sentinel lymphadenectomy in solid neoplasms.Cancer J 4, 351–8.
Boardman KC, Swartz MA (2003) Interstitial flow as a guide for lymphangiogenesis.Circ Res 92, 801–8.
Breiteneder-Geleff S, Matsui K, Soleiman Aet al. (1997) Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis.Am J Pathol 151, 1141–52.
Breiteneder-Geleff S, Soleiman A, Kowalski Het al. (1999) Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: Podoplanin as a specific marker for lymphatic endothelium.Am J Pathol 154, 385–94.
Bunone G, Vigneri P, Mariani Let al. (1999) Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features.Am J Pathol 155, 1967–76.
Cann SA, vanNetten JP, Ashby TLet al. (1995) Role of lymphangenesis in neovascularisation.Lancet 346, 388–90.
Cao Y, Linden P, Farmebo Jet al. (1998) Vascular endothelial growth factor C induced angiogenesisin vivo.Proc Natl Acad Sci, USA 95, 14 389–94.
Carreira CM, Nasser SM, diTomasoet al. (2000) LYVE-1 is not restricted to lymph vessels: Expression in normal liver sinusoids and down regulation in human liver cancer and cirrhosis.Cancer Res 61, 8079–84.
Castenholz A, Hauck G, Rettberg U (1991) Light and electron microscopy of the structural organization of the tissue- lymphatic fluid drainage system in the mesentery: An experimental study.Lymphology 24, 82–92.
Cursiefen C, Chen L, Borges LPet al. (2004) VEGF-A stimulates lymphangiogenesis and hemoangiogenesis in inflammatory neovascularrization via macrophage recruitment.J Clin Invest 113, 1040–50.
Dadras SS, Paul T, Bertoncini Jet al. (2003) Tumor lymphangio- genesis. A novel prognostic indicator for cutaneous melanoma metastasis and survival.Am J Pathol 162, 1951–60.
Dagenais SL, Hartsough RL, Erickson RPet al. (2004) Foxc2 is expressed in developing lymphatic vessels and other tissues associated with lymphedema-distichiasis syndrome.Gene Expr Patterns 4, 611–19.
Duff SE, Li C, Jeziorska Met al. (2003) Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy.Br J Cancer 89, 426–30.
Dumont DJ, Fong G, Puri PCet al. (1995) Vascularization of the mouse embryo: A study of flk-1, tek, tie, and vascular endothelial growth factor expression during development.Dev Dyn 203, 80–92.
Dumont DJ, Jussila L, Taipale J (1998) Cardiovascular failure in mouse embryos deficient in VEGF receptor-3.Science 282, 946–9.
Ezaki T, Kuwahara K (2002) Analysis of a specific marker for mouse lymphatics.Acta Anat Nipp 77 (Suppl.), 37 (Abstract).
Ezaki T, Matsuno K, Fujii Het al. (1990) A new approach for identification of rat lymphatic capillaries using a monoclonal antibody.Arch Histol Cytol 53 (Suppl.), 77–86.
Ezaki T, Kuwahara K, Morikawa Set al. (2004) Characterization of adjuvant-induced rat lymphangiomas as a model to study the lymph drainage from abdominal cavity.Jpn J Lymphol 27, 1–10.
Ferrara N (2004) Vascular endothelial growth factor: Basic science and clinical progress.Endocr Rev 25, 581–611.
Furudoi A, Tanaka S, Haruma Ket al. (2002) Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma.Oncology 62, 157–66.
Gale NW, Thurston G, Hackett SFet al. (2002) Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by angiopoietin-1.Dev Cell 3, 411–23.
Gould EA, Winship T, Philbin PHet al. (1960) Observation on a ‘sentinel node’ in cancer of the parotid.Cancer 13, 77–8.
Hall FT, Freeman JL, Asa SLet al. (2003) Intratumoral lymphatics and lymph node metastases in papillary thyroid carcinoma.Arch Otolaryngol Head Neck Surg 129, 716–19.
Hashimoto I, Kodama J, Seki Net al. (2001) Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer.Br J Cancer 85, 93–7.
He L, Papousti M, Hung Ret al. (2003) Three different fates of cells migrating from somites into the limb bud.Anat Embryol 207, 29–34.
He Y, Kozaki K, Kapanen Tet al. (2002) Supression of tumor lymphangiogenesis and lymph node metastasis by bloking vascular endothelial growth factor receptor 3 signaling.J Natl Cancer Inst 94, 819–25.
He Y, Rajantie I, Ilmonen Met al. (2004a) Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis.Cancer Res 64, 3737–40.
He Y, Karpanen T, Alitalo K (2004b) Role of lymphangiogenenic factors in tumor metastasis.Biochem Biophys Acta 1654, 3–12.
Hirai M, Nakagawara A, Oosaki Tet al. (2001) Expression of vascular endothelial growth factor (VEGF-A/VEGF-1 and VEGF-C/VEGF-2) in post menopausal uterine endothelial carcinoma.Gynecol Oncol 80, 181–8.
Hirakawa S, Kodama S, Kunstfeld Ret al. (2005) VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis.J Exp Med 201, 1089–99.
Hong YK, Harvey N, Noh YHet al. (2002) Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate.Dev Dyn 225, 351–7.
Hong YK, Lange-Asschenfeldt B, Velasco Pet al. (2004) VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the α1p1and α2β1 integrinsFASEB J 18, 1111–13.
Jackson DG, prevo R, Clasper S, Banerji S (2001) LYVE-1, the lymphatic system and tumor lymphangiogenesis.Trends Immunol 22, 317–21.
Ji RC, Kato S (2001) Histochemical analysis of lymphatic endothelial cells in lymphostasis.Microsc Res Tech 55, 70–80
Ji RC, Kato S (2003) Lymphatic network and lymphangiogenesis in the gastric wall.J Histochem Cytochem 51, 331–8
Ji RC, Miura M, Qu P, Kato S (2004) Expression of VEGFR-3 and 5’-Nase in regenerating lymphatic vessels of the cutaneous wound healing.Microsc Res Tech 64, 279–86
Jodanov DA (1996) On senile changes in lymphatic capillaries and vessels.J Cardiovasc Surg 7, 108–16
Joukov V, Pajusola K, Kaipainen A (1996) A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt-4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinasesEMBO J 15, 290–8
Jussila L, Alitalo K (2002) Vascular growth factors and lymphangiogenesis.Phsiol Rev 82, 673–700
Kaipainen A, Korhonen J, Pajusola Ket al. (1993) The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells.J Exp Med 178, 2077–88
Kaipainen A, Vlaykova T, Hatva Eet al. (1994) Enhanced expression of the receptor tyrosine kinase messenger RNA in the vascular endothelium of metastatic melanomasCancer Res 54, 6571–7
Kaipainen A, Korhonen J, Mustonen Tet al. (1995) Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.Proc Natl Acad Sci USA 92, 3566–70
Kajiya K, Hirokawa S, Ma Bet al. (2005) Hepatocyte growth factor promotes lymphatic vessel formation and functionEMBO J 24, 2885–95
Karkkainen MJ, Jussila L, Ferrell REet al. (2001) Molecular regulation of lymphangiogenesis and targets for tissue edema.Trends Mol Med 7, 18–22
Kato S (1990) Enzyme-histochemical identification of lymphatic vessels by light and backscattered image scanning electron microscopy.Stain Technol 65, 131–7.
Kato S (2000) Organ specificity of the structural organization and fine distribution of lymphatic capillary networks Histochemical study.Histol Histopathol 15, 185–97
Kato S (2003) Lymphatic endothelial cell markers and lymphangiogenesis.Jpn J Lymphol 26, 1–20 (in Japanese with an English abstract)
Kato S, Gotoh M (1990) Application of backscattered elecron imaging to enzyme histochemistry of lymphatic capillariesJ Electron Microsc 39, 186–90
Kato S, Miura M, Miyauchi R (1993) Structural organization of the initial lymphatics in the monkey mesentery and intestinal wall as revealed by an enzyme-histochemistry.Arch Histol Cytol 56, 149–60
Kato S, Itonaga I, Ji RCet al. (1996) Enzyme triple staining for differentiation of lymphatics from venous and arterial capillaries.Lymphology 29, 15–19
Katsuta M, Miyashita M, Makino Het al. (2005) Correlation of hypoxia inducible factor-1α with lymphatic metastasis via vascular endothelial growth factor-C in human esophageal cancer.Exp Mol Pathol 78, 123–30.
Kitagawa Y, Fujii H, Mukai Wet al. (2002) Radio-guided sentinel node detection for gastric cancer.Br J Surg 89, 604–8.
Kotani M (1990) The lymphatics and lymphoreticular tissues in relation to the action of sex hormones.Arch Histol Cytol 53 (Suppl.), 1–76.
Koukourakis MI, Giatromanolaki A, Sivridis Eet al. (2005) LYVE- 1 immunohistochemical assessment of lymphangiegenesis in endometrial and cancer.J Clin Pathol 58, 202–6.
Kukk E, Lymboussaki A, Taira Set al. (1996) VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development.Development 122, 3829–37.
Kukk E, Wartiovaara U, Gunji Yet al. (1997) Analysis of Tie receptor tyrosine kinase in haemopoietic progenitor and leukaemia cells.Br J Haematol 98, 195–203.
Kuwai T, Kitadai Y, Tanaka Set al. (2003) Expression of hypoxia- inducible factor 1 alpha is associated with tumor vascularization in human colorectal carcinoma.Int J Cancer 105, 176–81.
Kyzas P, Geleff S, Batistatou Aet al. (2005) Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma.J Pathol 206, 170–7.
Leak LV, Jones M (1994) Lymphangiogenesisin vitro: Formation of lymphatic capillary-like channels from confluent monolayers of lymphatic endothelial cells.In Vitro Cell Dev Biol Anim 30, 512–18.
Lee AK, DeLellis RA, Silverman MLet al. (1990) Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast.J Clin Oncol 8, 1457–65.
Leu AJ, Berk DA, Lymboussaki Aet al. (2000) Absence of functional lymphatics within a murine sarcoma: A molecular and functional evaluation.Cancer Res 61, 4324–7.
Lymboussaki A, Partanen TA, Olofsson B (1998) Expression of vascular endothelial growth factor C receptor VEGFR-3 in lymphatic endothelium for the skin and in vascular tumors.Am J Pathol 153, 395–403.
Lymboussaki A, Olofsson B, Eriksson U, Alitalo K (1999) Vascular endothelial growth factor (VEGF) and VEGF-C show overlapping binding sites in embryonic endothelia and distinct sites in differentiated adult endothelia.Circ Res 85, 992–9.
Mäkinen T, Jussila L, Veikkola Tet al. (2001) Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3.Nat Med 7, 199–205.
Mandriota S, Jussila L, Jeltsch Met al. (2001) Vascular endothelial growth factor-C medicated lymphangiogenesis promotes tumor metastasis.EMBO J 20, 672–82.
Maula SM, Luukkaa M, Grenman Ret al. (2003) Intratumoral lymphatics are essential for the metastic spread and prognosis in squamous cell carcinomas of the head and neck region.Cancer Res 63, 1920–6.
Mizuno R, Yokoyama Y, Ono Net al. (2003) Establishment of rat lymphatic endothelial cell line.Microcirculation 10, 127–31.
Morton DL, Wen DR, Wong JHet al. (1992) Technical details of intraoperative lymphatic mapping for early stage melanoma.Arch Surg 127, 392–9.
Niki T, Iba S, Tokunou Met al. (2000) Expression of vascular endothelial growth factors A, B, C and D and their relationships to lymph node status in lung adenocarcinoma.Clin Cancer Res 6, 2431–9.
Noguchi T, Takeno S, Shibata Tet al. (2002) VEGF-C expression correlates with histological differentiation and metastssis in squamous cell carcinoma of the esophagus.Oncol Rep 9, 995–9.
Oh SJ, Jeltsch MM, Birkengager R*et al. (1997) VEGF and VEGF-C: Specific induction of angiogenesis and lymphang- iogenesis in the differentiated avian chorioallantoic membrane.Dev Biol 188, 96–109.
Ohta Y, Nozawa H, Tanaka Yet al. (2000) Increased vascular endothelial growth factor and vascular endothelial growth factor-C and increased um23 expression associated with microdissemination in the lymph nodes in stage non-small cell lung cancer.J Thorac Cardiovasc Surg 119, 804–13.
Ohtani Y, Ohtani O (2001) Postnatal development of lymphatic vessels and their smooth muscle cells in the rat diaphragm: A confocal microscopic study.Arch Histol Cytol 64, 513–22.
Oliver G, Detmar M (2002) The rediscovery of the lymphatic system: Old and new insights into the development and biological function of the lymphatic vasculature.Gene Dev 16, 772–83.
Paavonen K, Puolakkainen P, Jussila Let al. (2000) Vascular endothelial growth factor-3 in lymphangiogenesis in wound healing.Am J Pathol 156, 1499–504.
Padera TP, Kadambi A, di Tomaso Eet al. (2002) Lymphatic metastasis in the absence of functional intratumor lymphatics.Science 296, 1883–6.
Papousti M, Tomarev SI, Eichmann Aet al. (2001) Endogeneous origin of the lymphatics in the avian chorioallantoic membrane.Dev Dyn 222, 238–51.
Pepper MS, Tille J-C, Nisato R, Skobe M (2003) Lymphangio- genesis and tumor metastasis.Cell Tissue Res 314, 167–77.
Petrova TV, Makinen T, Makela TPet al. (2002) Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor.EMBO J 21, 4593–9.
Petrova TV, Karpanen T, Norrmén Cet al. (2004) Defective valves and abdominal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis.Nat Med 10, 974–81.
Pytowski B, Goldman J, Persaud Ket al. (2005) Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing angibody.J Natl Cancer Inst 97, 14–21.
Saaristo A, Veikkola T, Tammela Tet al. (2002) Lymphangiogenic gene therapy with minimal blood vascular side effects.J Exp Med 196, 719–30.
Saaristo A, Tammela T, Timonen Jet al. (2004) Vascular endothelial growth factor-C gene therapy restores lymphatic flow across incision wounds.FASEB J 18, 1707–9.
Salven P, Lymboussaki A, Heikkila Pet al. (1998) Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors.Am J Pathol 153, 103–8.
Schacht V, Ramirez MI, Hong Y-Ket al. (2003) T1αpodoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema.EMBO J 22, 3546–56.
Schneider M, Othman-Hassan K, Crist Bet al. (1999) Lymphangioblasts in the avian wing bud.Dev Dyn 216, 311–19.
Sedivy R, Beck-Mannagetta J, Haverkampf Cet al. (2001) Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer.J Oral Pathol Med 32, 455–60.
Shao X-J, Ohtani O, Saitoh Met al. (1998) Development of diaphragmatic lymphatics: The process of their direct connection to the peritoneal cavity.Arch Histol Cytol 61, 137–49.
Shields JD, Borsetti M, Rigby Het al. (2004) Lymphatic density and metastatic spread in human malignant melanoma.Br J Cancer 90, 693–70.
Shimizu K, Kubo H, Ymaguchi Ket al. (2004) Supression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer.Cancer Res 95, 328–33.
Shimoda H, Takahashi Y, Kato S (2001) Development of the lymphatic network in the muscle coat of the rat jejunum as revealed by enzyme-histochemistry.Arch Histol Cytol 64, 523–33.
Shimoda H, Takahashi Y, Kajihara T, Kato S (2003) Demonstration of the ratlymphatic vessels using immunohistochemistry andin situ hybridization for 5’-nucleotidase.Biomed Res 24, 51–7.
Shimoda H, Takahashi Y, Kato S (2004) Regrowth of lymphatic vessels following transaction of the muscle coat in the rat small intestine.Cell Tissue Res 316, 325–38.
Skobe M, Hawighorst T, Jackson DGet al. (2001) Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis.Nat Med 7, 192–8.
Stacker S, Caesar C, Baldwin MEet al. (2001) VEGF-D promots the metastastic spread of tumor cells via the lymphatics.Nat Med 7, 186–91.
Swartz M, Skobe M (2001) Lymphatic function, lymphangiogenesis and cancer metastasis.Microsc Res Tech 55, 92–9.
Tan Y (1998) Basic fibroblast growth factor-midiated lymphang- iogenesis of lymphatic endothelial cells isolated from dog thoracic ducts: Effect of heparin.Jpn J Physiol 48, 133–41.
Tanigawa N, Kanazawa T, Satomura Ket al. (1981) Experimental- study on lymphatic vascular changes in the development of cancer.Lymphology 14, 149–54.
Travella W, Dugan MC (1990) Endothelial interactions. In:Progress in Lymphology, VII. (Nishi M, Uchino S, Yabuki Set al., eds). Elsevier Science, Amsterdam, 269–70.
Tsurusaki T, Kanda S, Sakai Het al. (1999) Vascular endothelial growth factor-C expression in human prostatic carcinoma andits relationship to lymph node metastasis.Br J Cancer 80, 309–13.
Valtola R, Salven P, Heikkila Pet al. (1999) VEGF-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer.Am J Pathol 154, 1381–90.
Veikkola T, Jussila I, Makinen Tet al. (2001) Signaling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice.EMBO J 20, 123–1.
Weninger W, PartanenT, Breiteneder-Geleff Set al. (1999) Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi’s sarcoma tumor cells.Lab Invest 78, 243–51.
Wigle JT, Oliver G (1999) Prox-1 function is required for the development of the murine lymphatic system.Cell 98, 769–78.
Wigle JT, Harvey N, Detmar Met al. (2002) An essential role forProx 1 in the induction of the lymphatic endothelial cell phenotype.EMBO J 21, 1505–13.
Williams CSM, Leek RD, Robson AMet al. (2003) Absence of lymphangiogenesis and intratumoural lymph vessels in human metastatic breast cancer.J Pathol 200, 195–206.
Wilting J, Christ B, Bokeloh Met al. (1991) A modified chorioal- lantoic membrane (CAM) assay for qualitative and quantitative study of growth factors. Studies on the effects of carriers, PBS, angiogenin, and bFGF.Anat Embryol 183, 259–71.
Wilting J, Eichmann A, Christ Bet al. (1997) Expression of the avian VEGF receptor homologues Quek 1 and Quek 2 in blood-vascular and lymphatic endothelial and nonendothelial cells during quail embryonic development.Cell Tissue Res 288, 207–23.
Wilting J, Kurz H, Oh STet al. (1998) Angiogenesis and lymphangiogenesis: Analogous mechanisms and homologous growth factors. In:Vascular Morphogenesis: In Vitro, In Vivo and In Mente (Little C, Mironov V, Sage H, eds). Birkhäusen, Bostone, 21–34.
Wilting J, Neeff H, Christ B (1999) Embryonic lymphangiogenesis.Cell Tissue Res 297, 1–11.
Wilting J, Tomarev SI, Christ B (2003) Lymphangioblasts in embryonic lymphangiogenesis.Lymphat Res Biol 1, 33–40.
Witte CL, Witte MH (1985) Lymphatics in pathophysiology of edema. In:Experimental Biology of the Lymphatic Circulation (Johnston MG, ed.). Elsevier, Amsterdam, 165–179.
Yamashita Y, Hooker SW, Jiang Het al. (1998) CD73 expression and fyn-dependent signaling on murine lymphocytes.Eur J Immunol 28, 2981–90.
Yonemura Y, Endo Y, Fujita Het al. (1999) Role of vascular endothelial growth factor C in the development of lymph node metastasis in gastric cancer.Clin Cancer Res 5, 1823–9.
Yonemura Y, Fushida S, Bando Eet al. (2001) Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3 in gastric cancer.Eur J Cancer 37, 918–23.
Yoon YS, Murayama T, Gravereaux Eet al. (2003) VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema.J Clin Invest 11, 717–25.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kato, S., Shimoda, H., Ji, RC. et al. Lymphangiogenesis and expression of specific molecules as lymphatic endothelial cell markers. Anato Sci Int 81, 71–83 (2006). https://doi.org/10.1111/j.1447-073X.2006.00142.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1447-073X.2006.00142.x