Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Apr;80(1-2):309–313. doi: 10.1038/sj.bjc.6690356

Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis

T Tsurusaki 1,2, S Kanda 1, H Sakai 1, H Kanetake 1, Y Saito 1, K Alitalo 3, T Koji 2
PMCID: PMC2362987  PMID: 10390013

Abstract

Lymph node dissemination is a major prognostic factor in human cancer. However, the molecular mechanisms underlying lymph node metastasis are poorly understood. Recently, vascular endothelial growth factor-C (VEGF-C) was identified as a ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and the expression of VEGFR-3 was found to be highly restricted to the lymphatic endothelial cells. In this report, we investigated the expression of VEGF-C and VEGFR-3 in human prostatic carcinoma tissue by using in situ hybridization and immunohistochemical staining respectively. Expression of VEGF-C mRNA in prostatic carcinoma was significantly higher in lymph node-positive group than in lymph node-negative group. In addition, the number of VEGFR-3-positive vessels was increased in stroma surrounding VEGF-C-positive prostatic carcinoma cells. These results suggest that the expression of VEGF-C in prostatic carcinoma cells is implicated in the lymph node metastasis. © 1999 Cancer Research Campaign

Keywords: prostatic carcinoma, vascular endothelial growth factor-C, VEGF receptor-3, lymph node metastasis

Full Text

The Full Text of this article is available as a PDF (328.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Achen M. G., Jeltsch M., Kukk E., Mäkinen T., Vitali A., Wilks A. F., Alitalo K., Stacker S. A. 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 U S A. 1998 Jan 20;95(2):548–553. doi: 10.1073/pnas.95.2.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams J. C. Heavy metal intensification of DAB-based HRP reaction product. J Histochem Cytochem. 1981 Jun;29(6):775–775. doi: 10.1177/29.6.7252134. [DOI] [PubMed] [Google Scholar]
  3. Barleon B., Sozzani S., Zhou D., Weich H. A., Mantovani A., Marmé D. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood. 1996 Apr 15;87(8):3336–3343. [PubMed] [Google Scholar]
  4. Clauss M., Weich H., Breier G., Knies U., Röckl W., Waltenberger J., Risau W. The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem. 1996 Jul 26;271(30):17629–17634. doi: 10.1074/jbc.271.30.17629. [DOI] [PubMed] [Google Scholar]
  5. Dvorak H. F., Brown L. F., Detmar M., Dvorak A. M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995 May;146(5):1029–1039. [PMC free article] [PubMed] [Google Scholar]
  6. Epstein J. I., Partin A. W., Sauvageot J., Walsh P. C. Prediction of progression following radical prostatectomy. A multivariate analysis of 721 men with long-term follow-up. Am J Surg Pathol. 1996 Mar;20(3):286–292. doi: 10.1097/00000478-199603000-00004. [DOI] [PubMed] [Google Scholar]
  7. Ferrara N., Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4–25. doi: 10.1210/edrv.18.1.0287. [DOI] [PubMed] [Google Scholar]
  8. Folkman J., Shing Y. Angiogenesis. J Biol Chem. 1992 Jun 5;267(16):10931–10934. [PubMed] [Google Scholar]
  9. Fong G. H., Rossant J., Gertsenstein M., Breitman M. L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 1995 Jul 6;376(6535):66–70. doi: 10.1038/376066a0. [DOI] [PubMed] [Google Scholar]
  10. Jeltsch M., Kaipainen A., Joukov V., Meng X., Lakso M., Rauvala H., Swartz M., Fukumura D., Jain R. K., Alitalo K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997 May 30;276(5317):1423–1425. doi: 10.1126/science.276.5317.1423. [DOI] [PubMed] [Google Scholar]
  11. Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E., Saksela O., Kalkkinen N., Alitalo K. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996 Jan 15;15(2):290–298. [PMC free article] [PubMed] [Google Scholar]
  12. Jussila L., Valtola R., Partanen T. A., Salven P., Heikkilä P., Matikainen M. T., Renkonen R., Kaipainen A., Detmar M., Tschachler E. Lymphatic endothelium and Kaposi's sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Res. 1998 Apr 15;58(8):1599–1604. [PubMed] [Google Scholar]
  13. Kaipainen A., Korhonen J., Mustonen T., van Hinsbergh V. W., Fang G. H., Dumont D., Breitman M., Alitalo K. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3566–3570. doi: 10.1073/pnas.92.8.3566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koji T., Nakane P. K. Recent advances in molecular histochemical techniques: in situ hybridization and southwestern histochemistry. J Electron Microsc (Tokyo) 1996 Apr;45(2):119–127. doi: 10.1093/oxfordjournals.jmicro.a023420. [DOI] [PubMed] [Google Scholar]
  15. Oh S. J., Jeltsch M. M., Birkenhäger R., McCarthy J. E., Weich H. A., 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 Aug 1;188(1):96–109. doi: 10.1006/dbio.1997.8639. [DOI] [PubMed] [Google Scholar]
  16. Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L., Alitalo R., Alitalo K. FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res. 1992 Oct 15;52(20):5738–5743. [PubMed] [Google Scholar]
  17. Shalaby F., Rossant J., Yamaguchi T. P., Gertsenstein M., Wu X. F., Breitman M. L., Schuh A. C. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995 Jul 6;376(6535):62–66. doi: 10.1038/376062a0. [DOI] [PubMed] [Google Scholar]
  18. Slack N. H., Lane W. W., Priore R. L., Murphy G. P. Prostatic cancer. Treated at a categorical center, 1980-1983. Urology. 1986 Mar;27(3):205–213. doi: 10.1016/0090-4295(86)90276-1. [DOI] [PubMed] [Google Scholar]
  19. Steiner M. S. Role of peptide growth factors in the prostate: a review. Urology. 1993 Jul;42(1):99–110. doi: 10.1016/0090-4295(93)90352-b. [DOI] [PubMed] [Google Scholar]
  20. Tsurusaki T., Koji T., Sakai H., Kanetake H., Nakane P. K., Saito Y. Cellular expression of beta-microseminoprotein (beta-MSP) mRNA and its protein in untreated prostate cancer. Prostate. 1998 May;35(2):109–116. doi: 10.1002/(sici)1097-0045(19980501)35:2<109::aid-pros4>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  21. Waltenberger J., Claesson-Welsh L., Siegbahn A., Shibuya M., Heldin C. H. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem. 1994 Oct 28;269(43):26988–26995. [PubMed] [Google Scholar]
  22. Yoshii A., Koji T., Ohsawa N., Nakane P. K. In situ localization of ribosomal RNAs is a reliable reference for hybridizable RNA in tissue sections. J Histochem Cytochem. 1995 Mar;43(3):321–327. doi: 10.1177/43.3.7532657. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES