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The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer
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  • Regular Article
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  • Published: 17 July 2001

The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer

  • T Kajita1,
  • Y Ohta1,
  • K Kimura1,
  • M Tamura1,
  • Y Tanaka1,
  • Y Tsunezuka1,
  • M Oda1,
  • T Sasaki2 &
  • …
  • Go Watanabe1 

British Journal of Cancer volume 85, pages 255–260 (2001)Cite this article

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Abstract

Expression of vascular endothelial growth factor (VEGF)-C and that of its receptors were assessed in non-small cell lung cancer. Immunohistochemistry revealed positive VEGF-C expression in 38.7% (24/62) of the patients studied. A significant positive correlation was found between VEGF-C in cancer cells and VEGF receptor-3 (VEGFR-3) in vascular endothelial cells, but not between VEGF-C in cancer cells and VEGFR-2 in endothelial cells. In this cohort of lung cancer patients, VEGF-C expression was significantly associated with lymph node metastasis, lymphatic vessel invasion, and worse outcomes after the operation. Although the independent prognostic impact of VEGF-C and VEGFR-3 was not clear, VEGFR-2 expression in endothelial cells retained the independency as the prognostic indicator. In light of these findings, we conclude that VEGF-C plays an important role in lymphatic invasion/metastasis and tumour progression in non-small cell lung cancer. © 2001 Cancer Research Campaign www.bjcancer.com

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Achen MG, Jeltsch M, Kukk E, Makinen T, Vitali A, Wilks AF, Alitalo K and Stacker SA (1998) Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor-2 (Flk-1) and VEGF receptor-3 (Flt-4). Proc Natl Acad Sci USA 95: 548–553

    Article  CAS  Google Scholar 

  • Akagi K, Ikeda Y, Miyazaki M, Abe T, Kinoshita J, Maehara Y and Sugimachi K (2000) Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues. Br J Cancer 83: 887–891

    Article  CAS  Google Scholar 

  • Boocock CA, Charnock-Jones DS, Sharkey AM, McLaren J, Barker PJ, Wright KA, Twentyman PR and Smith SK (1995) Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma. J Nat Cancer Inst 87: 506–516

    Article  CAS  Google Scholar 

  • Cao Y, Linden P, Farnebo J, Cao R, Eriksson A, Kumar V, Qi JH, Claesson WL and Alitalo K (1998) Vascular endothelial growth factor C induces angiogenesis in vivo. Proc Natl Acad Sci USA 95: 14389–14394

    Article  CAS  Google Scholar 

  • Decaussin M, Sartelet H, Robert C, Moro D, Claraz C, Brambilla C and Brambilla E (1999) Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt-1 and VEGF-R2 Flk1/KDR) in non-small cell lung carcinomas (NSCLCs). J Pathol 188: 369–377

    Article  CAS  Google Scholar 

  • Ferrara N and Davis-Smyth, (1997) The biology of vascular endothelial growth factor. Endocrine Rev 18: 4–25

    Article  CAS  Google Scholar 

  • Ferrer FA, Miller LJ, Lindquist R, Kowalczyk P, Laudone VP, Albertsen PC and Kreutzer DL (1999) Expression of vascular endothelial growth factor receptors in human prostete cancer. Urology 54: 567–572

    Article  CAS  Google Scholar 

  • Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med 1: 27–31

    Article  CAS  Google Scholar 

  • Gitay-Goren H, Halaban R and Neufeld G (1993) Human melanoma cells but not normal melanocytes express vascular endothelial growth factor receptors. Biochem Biophys Res Commun 190: 702–708

    Article  CAS  Google Scholar 

  • Joukov V, Pajusola K, Kaipaien A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N and Alitalo K (1996) A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt-4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 15: 290–298

    Article  CAS  Google Scholar 

  • Jussila L, Valtola R, Partanen TA, Salven P, Heikkila P, Matikainen M-T, Renkonen R, Kaipainen A, Detmar M, Tschachler E, Alitalo R and Alitalo K (1998) Lymphatic endothelium and Kaposi’s sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Res 58: 1599–1604

    CAS  Google Scholar 

  • Lu Q and Brodie A (1996) Stimulation of the growth of MCF-7 and MDA MB-468 breast cancer cells by vaslular endothelial growth factor. Proc Am Assoc Cancer Res 37: 1499

    Google Scholar 

  • Lymboussaki A, Partanen TA, Olofsson B, Thomas-Crusells J, Fletcher C, deWaal R, Kaipainen A and Alitalo K (1998) Expression of the vascular endothelial growth factor C receptor VEGFR-3 in lymphatic endothelium of the skin and in vascular tumors. Am J Pathol 153: 395–403

    Article  CAS  Google Scholar 

  • Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, Banerji S, Huarte J, Montesano R, Jackson DG, Orci L, Alitalo K, Christofori G and Pepper MS (2001) Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 20: 672–682

    Article  CAS  Google Scholar 

  • Meyer M, Clauss M, Lepple-Wienhues A, Waltenberger J, Augustin HG, Ziche M, Lanz C, Buttner M, Rziha HJ and Dehio C (1999) A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases. EMBO J 18: 363–374

    Article  CAS  Google Scholar 

  • Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y and Hirohashi S (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: 2431–2439

    CAS  Google Scholar 

  • Ohta Y, Shridhar V, Bright RK, Kalemkerian GP, Du W, Carbone M, Watanabe Y and Pass HI (1999) VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. Br J Cancer 81: 54–61

    Article  CAS  Google Scholar 

  • Pajusola K, Aprelikova O, Korhonen J, Kaipainen A, Pertovaara L, Alitalo R and Alitalo K (1992) FLT-4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res 52: 5738–5743

    CAS  PubMed  Google Scholar 

  • Skobe M, Hawighorst T, Jackson D, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K and Detmar M (2001) Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nature med 7: 192–198

    Article  CAS  Google Scholar 

  • Speirs V and Atkin SL (1999) Production of VEGF and expression of the VEGF receptors Flt-1 and KDR in primary cultures of epithelial and stromal cells derived from breast tumours. Br J Cancer 80: 898–903

    Article  CAS  Google Scholar 

  • Tsurusaki T, Kanda S, Sakai H, Kanetake H, Saito Y, Alitalo K and Koji T (1999) Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis. Br J Cancer 80: 309–313

    Article  CAS  Google Scholar 

  • Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M and Heldin CH (1994) Different signal transduction properties of KDR and Flt-1, two receptors for vascular endothelial growth factor. J Biol Chem 269: 26988–26995

    CAS  PubMed  Google Scholar 

  • Xie B, Tam NNC, Tsao SW and Wong YC (1999) Co-expression of vascular endothelial growth factor (VEGF) and its receptors (flk-1 and flt-1) in hormone induced mammary cancer in the Noble rat. Br J Cancer 81: 1335–1343

    Article  CAS  Google Scholar 

  • Yonekura H, Sakurai S, Liu X, Migita H, Wang H, Yamagishi S, Nomura M, Abedin MJ, Unoki H, Yamamoto Y and Yamamoto H (1999) Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis. J Biol Chem 274: 35172–35178

    Article  CAS  Google Scholar 

  • Yonemura Y, Endo Y, Fujita H, Fushida S, Ninomiya I, Bandou E, Taniguchi K, Miwa K, Ohoyama S, Sugiyama K and Sasaki T (1999) Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin Cancer Res 5: 1823–1829

    CAS  Google Scholar 

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Authors and Affiliations

  1. First Department of Surgery, Kanazawa University School of Medicine, Takara-machi 13-1, Kanazawa, 920-8641, Japan

    T Kajita, Y Ohta, K Kimura, M Tamura, Y Tanaka, Y Tsunezuka, M Oda & Go Watanabe

  2. Department of Experimental Therapeutics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

    T Sasaki

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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Kajita, T., Ohta, Y., Kimura, K. et al. The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer. Br J Cancer 85, 255–260 (2001). https://doi.org/10.1054/bjoc.2001.1882

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  • Received: 24 October 2000

  • Revised: 27 March 2001

  • Accepted: 27 March 2001

  • Published: 17 July 2001

  • Issue date: 20 July 2001

  • DOI: https://doi.org/10.1054/bjoc.2001.1882

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Keywords

  • VEGF-C
  • lung cancer
  • lymph node metastasis
  • VEGFR

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