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Role of VEGF-C and VEGF-D in lymphangiogenesis in gastric cancer

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Abstract

Background

The molecular mechanisms of lymphangiogenesis induced by vascular endothelial growth factor (VEGF)-C and VEGF-D in gastric cancer were studied.

Methods

VEGF-C and VEGF-D gene expression vectors were transfected into the gastric cancer cell line KKLS, which did not originally express VEGF-C and VEGF-D, and stable transfectants (KKLS/VEGF-C and KKLS/VEGF-D) were established. The cell lines were inoculated into the subserosal layer of the stomach and subcutaneous tissue of nude mice.

Results

VEGF-C and VEGF-D expression in KKLS/VEGF-C and KKLS/VEGF-D cells was found by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Expression of mouse VEGF receptor (VEGFR)-2 and mouse VEGFR-3 mRNA was detected in the KKLS/VEGF-C and KKLS/VEGF-D gastric tumors. Newly formed lymphatic vessels were detected not only in the periphery but also in the center of the tumors. The intratumor lymphatic vessels connected with the preexisting lymphatic vessels in the muscularis mucosa. The average numbers of lymphatic vessels in KKLS/VEGF-C (52.0 ± 9.5) and KKLS/VEGF-D (16.4 ± 0.6) gastric tumors were significantly higher than that in the KKLS/control vector tumors (4.0 ± 1.4).

Conclusion

VEGF-C and VEGF-D may induce neoformation of lymphatic vessels in experimental gastric tumors by the induction of VEGFR-3 expression.

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Authors and Affiliations

  1. Gastric Surgery Division, Shizuoka Cancer Center, 1007 Shimo-Nagakubo, Nagaizumi-Machi, Shizuoka, 411-8777, Japan

    Yutaka Yonemura, Taiichi Kawamura & Etsurou Bandou

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

    Yoshio Endo, Kayoko Tabata & Takuma Sasaki

  3. Chungbuk University, Department of Surgery, Chungbuk, Korea

    Hyo-Yung Yun

  4. Department of Anatomy, Oita Medical University, Oita, Japan

    Masahiro Miura

Authors
  1. Yutaka Yonemura
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  2. Yoshio Endo
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  3. Kayoko Tabata
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  4. Taiichi Kawamura
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  5. Hyo-Yung Yun
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  6. Etsurou Bandou
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  7. Takuma Sasaki
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  8. Masahiro Miura
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Correspondence to Yutaka Yonemura.

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Yonemura, Y., Endo, Y., Tabata, K. et al. Role of VEGF-C and VEGF-D in lymphangiogenesis in gastric cancer. Int J Clin Oncol 10, 318–327 (2005). https://doi.org/10.1007/s10147-005-0508-7

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  • DOI: https://doi.org/10.1007/s10147-005-0508-7

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