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Tumor self-seeding by circulating tumor cells in nude mouse models of human osteosarcoma and a preliminary study of its mechanisms

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Abstract

Purpose

The purpose of this study is to determine whether and how tumor self-seeding by circulating tumor cells (CTCs) plays a role in the initiation and progression of osteosarcoma.

Methods

Two different nude mouse models of human osteosarcoma were established for detecting tumor self-seeding by fluorescently labeled CTCs. Various tumor growth indicators were quantitated for seeded and unseeded groups. Growth mechanisms were characterized using cell proliferation assays and immunohistochemical staining. Conditioned media of primary osteosarcoma cells was characterized in a Transwell migration assay and enzyme-linked immunosorbent assay. The effect of cytokines secreted by primary tumor cells was verified by small interfering RNA and recombinant human cytokine experiments.

Results

Red fluorescent protein-labeled CTCs seeded primary tumors in both models. Seeded primary tumors groups grew faster than control groups (P < 0.05), which was partially attributed to the CTCs having a higher proliferation rate and higher vascular endothelial growth factor expression after self-seeding. Conditioned media of primary osteosarcoma cells attracted CTCs, through an IL-6-dependent mechanism.

Conclusions

CTC tumor self-seeding occurs in osteosarcoma and promotes the growth of primary osteosarcoma. CTCs appear to be recruited by cytokines secreted by primary osteosarcoma cells, particularly IL-6.

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Acknowledgments

This research was financially supported by National Natural Science Foundation of China (No. 81372297, 30973409, 81201633).

Conflict of interest

The authors have declared that no conflict of interests exist.

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Authors and Affiliations

  1. Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China

    Yinglong Zhang, Qiong Ma, Tao Liu, Kuo Jiang, Yanhua Wen, Baoan Ma, Yong Zhou, Qingyu Fan & Xiuchun Qiu

  2. Frensley Center for Imaging Research, Department of Radiology, Baylor College of Medicine, Houston, TX, USA

    Shi Ke

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  1. Yinglong Zhang
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  2. Qiong Ma
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  4. Shi Ke
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  6. Yanhua Wen
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  7. Baoan Ma
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  8. Yong Zhou
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  9. Qingyu Fan
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Corresponding authors

Correspondence to Qingyu Fan or Xiuchun Qiu.

Additional information

Yinglong Zhang, Qiong Ma and Tao Liu have contributed equally to this work.

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Zhang, Y., Ma, Q., Liu, T. et al. Tumor self-seeding by circulating tumor cells in nude mouse models of human osteosarcoma and a preliminary study of its mechanisms. J Cancer Res Clin Oncol 140, 329–340 (2014). https://doi.org/10.1007/s00432-013-1561-7

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  • DOI: https://doi.org/10.1007/s00432-013-1561-7

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