J Cancer 2017; 8(10):1786-1794. doi:10.7150/jca.17859

Research Paper

Bone Marrow Derived Mesenchymal Stem Cells Involve in the Lymphangiogenesis of Lung Cancer and Jinfukang Inhibits the Involvement In Vivo

Xian-Mei Zhou1✉, Dan Wang1, Hai-Lang He1, Jie Tang1, Jing Wu2, Ling Xu3✉, Jian-Xin Li2✉

1. Department of Respiratory Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China;
2. State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China;
3. Tumor Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China

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Zhou XM, Wang D, He HL, Tang J, Wu J, Xu L, Li JX. Bone Marrow Derived Mesenchymal Stem Cells Involve in the Lymphangiogenesis of Lung Cancer and Jinfukang Inhibits the Involvement In Vivo. J Cancer 2017; 8(10):1786-1794. doi:10.7150/jca.17859. Available from http://www.jcancer.org/v08p1786.htm

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Lymphangiogenesis plays an important role in cancer metastasis. Bone marrow-derived mesenchymal stem cells (BMMSCs) migrate to the site of tumorigenesis and in turn promote the metastasis. However, whether BMMSCs involve in the lymphangiogenesis of lung cancer is unclear. Jinfukang has clinically been used for the treatment of non small cell lung cancer (NSCLC) in China. In this study, to investigate the involvement of BMMSCs in lymphangiogenesis in lung cancer, and evaluate the inhibitory effect of Jinfukang on the lymphangiogenesis, chimeric mice were prepared by transplanting bone marrow from green fluorescent protein (GFP) transgenic mice (C57BL/6-EGFP) into irradiated C57BL/6 mice. Then, the chimeric mice were injected subcutaneously with freshly prepared Lewis lung carcinoma cell suspension to make lung tumor model, and the model mice were further orally administrated with Jinfukang once per day for 3 weeks. Four weeks after the bone marrow transplantation, GFP-positive cells primarily existed in bone marrow of acceptor mice, and three more weeks after, Lewis lung carcinoma cells formed a tumor mass in chimeric mice. Observation of GFP-positive cells revealed that BMMSCs transferred into the lung tumor. Immunofluorescent analyses of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), a lymphatic endothelium marker, demonstrated a part of lymphatic endothelial cells in lung cancer were derived from BMMSCs, and those lymphatic endothelial cells contributed to the lung tumor lymphangiogenesis. Furthermore, Jinfukang treatment resulted in a significant reduction of the average weight of the tumor mass in chimeric mice, and displayed a significant lower number of LYVE-1 positive cells. The present results suggest that BMMSCs transfer to tumor, differentiate into lymphatic endothelial cells, and involve in the lymphangiogenesis in lung cancer of mice. Jinfukang inhibits the lung tumor mass via suppression of the BMMSCs transformation and lung tumor lymphangiogenesis. Our findings might provide the potential for the cancer therapies.

Keywords: bone marrow-derived mesenchymal stem cells, chimeric mice, lung cancer, lymphangiogenesis, Jinfukang