CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF

  • Authors:
    • Peng Zhang
    • Ling Dong
    • Kang Yan
    • Hua Long
    • Tong-Tao Yang
    • Ming-Qing Dong
    • Yong Zhou
    • Qing-Yu Fan
    • Bao-An Ma
  • View Affiliations

  • Published online on: July 17, 2013     https://doi.org/10.3892/or.2013.2619
  • Pages: 1753-1761
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Chemokines and chemokine receptor 4 (CXCR4) play an important role in metastasis. CXCR4 is also expressed in the human osteosarcoma cell line 9607-F5M2 (F5M2), which has a high tumorigenic ability and potential for spontaneous pulmonary metastasis. Mesenchymal stem cells (MSCs) contribute to the formation of the tumor stroma and promote metastasis. However, mechanisms underlying the promotion of osteosarcoma growth and pulmonary metastasis by MSCs are still elusive. Our study co-injected the human MSCs and F5M2 cells into the caudal vein of nude mice. The total number of tumor nodules per lung was significantly increased in the F5M2+MSC group compared to the other groups (control, F5M2 cells alone and MSCs alone) at week six. Moreover, a high number of Dil-labeled MSCs was present also at the osteosarcoma metastasis sites in the lung. Using Transwell assays, we found that F5M2 cells migrate towards MSCs, while the CXCR4 inhibitor AMD3100 decreased the migration potential of F5M2 cells towards MSCs. Furthermore, upon treatment with F5M2-conditioned medium, MSCs expressed and secreted higher levels of VEGF as determined by immunohistochemistry, western blotting and ELISA, respectively. Importantly, co-cultured with F5M2 cells, MSCs expressed and secreted higher VEGF levels, while AMD3100 dramatically decreased the VEGF secretion by MSCs. However, CXCR4 expression on F5M2 cells was not significantly increased in the co-culture system. Additionally, VEGF increased the proliferation of both MSCs and F5M2 cells. These findings suggest that CXCR4-mediated osteosarcoma growth and pulmonary metastasis are promoted by MSCs through VEGF.
View Figures
View References

Related Articles

Journal Cover

October 2013
Volume 30 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang P, Dong L, Yan K, Long H, Yang T, Dong M, Zhou Y, Fan Q and Ma B: CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF. Oncol Rep 30: 1753-1761, 2013
APA
Zhang, P., Dong, L., Yan, K., Long, H., Yang, T., Dong, M. ... Ma, B. (2013). CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF. Oncology Reports, 30, 1753-1761. https://doi.org/10.3892/or.2013.2619
MLA
Zhang, P., Dong, L., Yan, K., Long, H., Yang, T., Dong, M., Zhou, Y., Fan, Q., Ma, B."CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF". Oncology Reports 30.4 (2013): 1753-1761.
Chicago
Zhang, P., Dong, L., Yan, K., Long, H., Yang, T., Dong, M., Zhou, Y., Fan, Q., Ma, B."CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF". Oncology Reports 30, no. 4 (2013): 1753-1761. https://doi.org/10.3892/or.2013.2619