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The chemokine receptor CXCR7 is a critical regulator for the tumorigenesis and development of papillary thyroid carcinoma by inducing angiogenesis in vitro and in vivo

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Tumor Biology

Abstract

Papillary thyroid carcinoma (PTC) is a well-differentiated neoplasm, but it can transfer early to cervical lymph nodes. Accumulating evidences have confirmed the important roles of CXCR7 in tumor cell proliferation, invasion, metastasis, and angiogenesis. Our previous study demonstrated CXCR7 modulated proliferation, apoptosis, and invasion of PTC cells. In this study, we evaluated the effect of expression of CXCR7 in PTC cells on angiogenesis and whether its expression had an influence on the tumor growth of PTC in vivo. We evaluated the effect of CXCR7 on interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) secretion, angiogenesis, and tumor growth by ELISA, endothelial tube formation assay, and a xenograft tumor model in nude mice. Immunohistochemistry was used to assess expression of CD34 in tumor of mice. In vitro and in vivo studies in PTC cells suggested that the alteration of CXCR7 expression was correlated with angiogenesis and tumor growth. Moreover, CXCR7 mediated the expression of IL-8 and VEGF, which might be involved in the regulation of tumor angiogenesis. These findings suggest that CXCR7 affects the growth of PTC cells and participates in the tumorigenesis of PTC, probably through regulating angiogenesis by the proangiogenic VEGF or IL-8.

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Acknowledgments

This project was supported by the National Nature Science Foundation of China (81072182) and Liaoning Provincial Nature Science Foundation (2013021100).

Authors’ contributions

Liu Z designed the study and revised the manuscript. Zhang HW and Yang L performed the experiments except ELISA and immunohistochemistry assay, and drafted the manuscript. Teng XY and Liu ZY performed the ELISA and immunohistochemistry assay. Liu CX and Zhang L participated in the experiments and performed data statistics. All authors read and approved the final manuscript.

Compliance with ethical standards

ᅟ

Ethical approval

All procedures performed in this study involving animals were in accordance with the ethical standards of the institution in the Affiliated Sheng**g Hospital of China Medical University.

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Authors and Affiliations

  1. Department of General Surgery, Sheng**g Hospital, China Medical University, No. 36 Sanhao Street, Shenyang, 110004, China

    Hengwei Zhang, Xuyong Teng, Zhangyi Liu, Chenxi Liu, Lei Zhang & Zhen Liu

  2. Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang, 110001, China

    Lei Yang

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  1. Hengwei Zhang
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  2. Lei Yang
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  3. Xuyong Teng
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  7. Zhen Liu
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Correspondence to Zhen Liu.

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Zhang, H., Yang, L., Teng, X. et al. The chemokine receptor CXCR7 is a critical regulator for the tumorigenesis and development of papillary thyroid carcinoma by inducing angiogenesis in vitro and in vivo. Tumor Biol. 37, 2415–2423 (2016). https://doi.org/10.1007/s13277-015-4051-5

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  • DOI: https://doi.org/10.1007/s13277-015-4051-5

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