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Human gastric cancer organizes neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells

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Abstract

Background

Lymphatic metastasis is a critical determinant of prognosis in human gastrointestinal cancers. Studies suggest that lymphatic metastasis has been linked to lymphangiogenesis, the growth of lymphatic vessels, while the mechanisms of tumor lymphangiogenesis remain poorly characterized.

Methods

Human gastric cancer cells, MKN45, were implanted under the gastric submucosa of nude mice receiving green fluorescent protein-positive bone marrow (BM) transplants. In addition, MKN45 cells were subcutaneously injected into the back of each mouse as a model of human tumor xenografts. The tumor tissue was analyzed 3 weeks after implantation.

Results

The mice with MKN45 cells represent recruitment and incorporation of BM-derived lymphatic endothelial progenitor cells (LEPC) into gastric lymphatics. Moreover, in a xenograft model, MKN45 cells induced lymphangiogenesis as well as recruitment of BM-derived LEPC in tumor lymphatics in a xenograft model.

Conclusions

These findings of this study suggest that human gastric adenocarcinoma induces tumor lymphangiogenesis via recruitment of LEPC from BM.

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Fig. 1

Abbreviations

GFP:

Green fluorescence protein

BM:

Bone marrow

LEPC:

Lymphatic endothelial progenitor cells

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Acknowledgments

This study was supported by a NaSNeLC research grant from Gifu University Graduate School of Medicine to S. Hayashi and M. Tawada, and the grants-in-aid from the Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology to S. Hayashi. We wish to thank Dr. Yosuke Osawa, Dr. Genzo Takemura, and Dr. Shinya Minatoguchi for technical support with the murine radiation systems.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departments of Surgical Oncology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan

    Masahiro Tawada, Shinji Osada & Kazuhiro Yoshida

  2. Department of Cell Signaling, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan

    Shin-ichiro Hayashi & Shigeru Nakashima

  3. Division of Hypertension and Nephrology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan

    Shin-ichiro Hayashi

Authors
  1. Masahiro Tawada
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  2. Shin-ichiro Hayashi
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  3. Shinji Osada
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  4. Shigeru Nakashima
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  5. Kazuhiro Yoshida
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Corresponding author

Correspondence to Shin-ichiro Hayashi.

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Tawada, M., Hayashi, Si., Osada, S. et al. Human gastric cancer organizes neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells. J Gastroenterol 47, 1057–1060 (2012). https://doi.org/10.1007/s00535-012-0638-4

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  • DOI: https://doi.org/10.1007/s00535-012-0638-4

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