Human gastric cancer organizes neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells
- 312 Downloads
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.
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.
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.
These findings of this study suggest that human gastric adenocarcinoma induces tumor lymphangiogenesis via recruitment of LEPC from BM.
KeywordsHuman gastric cancer Lymphatic endothelial progenitor cells Lymphangiogenesis Bone marrow
Green fluorescence protein
Lymphatic endothelial progenitor cells
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.