Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer

  • Authors:
    • Zofia Von Marschall
    • Arne Scholz
    • Steven A. Stacker
    • Marc G. Achen
    • David G. Jackson
    • Frauke Alves
    • Michael Schirner
    • Martin Haberey
    • Karl-Heinz Thierauch
    • Bertram Wiedenmann
    • Stefan Rosewicz
  • View Affiliations

  • Published online on: September 1, 2005     https://doi.org/10.3892/ijo.27.3.669
  • Pages: 669-679
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Abstract

The presence of lymphatic metastases is a strong indicator for poor prognosis in patients with ductal pancreatic cancer. In order to better understand the mechanisms controlling lymphatic growth and lymph node metastasis in human ductal pancreatic cancer, we analyzed the expression pattern of the vascular endothelial growth factor-D (VEGF-D), its receptor VEGF-receptor-3 (VEGFR-3) and the lymphatic endothelium-specific hyaluronan receptor LYVE-1 in a panel of 19 primary human ductal pancreatic tumors and 10 normal pancreas specimens. We further addressed the biological function of VEGF-D for induction of lymphatic metastasis in a nude mouse xenograft model using two human ductal pancreatic cancer cell lines with overexpression of VEGF-D. Compared to normal human pancreas, pancreatic cancer tissue showed overexpression of VEGF-D and VEGFR-3 in conjunction with a high lymphatic vascularization as determined by immunohistochemistry and in situ hybridization. Tumors derived from VEGF-D-overexpressing cells had a higher microvessel density compared to their mock-controls, as determined based on CD31 immunohistochemistry. Importantly, these tumors also revealed a significant induction of intra- and peritumoral lymphatics, as judged from immunohistochemical detection of LYVE-1 expression. This was associated with a significant increase in lymphatic vessel invasion by tumor cells and an increased rate of lymphatic metastases, as indicated by pan-cytokeratin reactive cells in lymph nodes. Our results suggest that VEGF-D plays a pivotal role in stimulating lymphangiogenesis and lymphatic metastasis in human ductal pancreatic cancer, and therefore represents a novel therapeutic target for this devastating disease.

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September 2005
Volume 27 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Von Marschall Z, Scholz A, Stacker SA, Achen MG, Jackson DG, Alves F, Schirner M, Haberey M, Thierauch K, Wiedenmann B, Wiedenmann B, et al: Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. Int J Oncol 27: 669-679, 2005.
APA
Von Marschall, Z., Scholz, A., Stacker, S.A., Achen, M.G., Jackson, D.G., Alves, F. ... Rosewicz, S. (2005). Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. International Journal of Oncology, 27, 669-679. https://doi.org/10.3892/ijo.27.3.669
MLA
Von Marschall, Z., Scholz, A., Stacker, S. A., Achen, M. G., Jackson, D. G., Alves, F., Schirner, M., Haberey, M., Thierauch, K., Wiedenmann, B., Rosewicz, S."Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer". International Journal of Oncology 27.3 (2005): 669-679.
Chicago
Von Marschall, Z., Scholz, A., Stacker, S. A., Achen, M. G., Jackson, D. G., Alves, F., Schirner, M., Haberey, M., Thierauch, K., Wiedenmann, B., Rosewicz, S."Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer". International Journal of Oncology 27, no. 3 (2005): 669-679. https://doi.org/10.3892/ijo.27.3.669