Open Access

M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF

  • Authors:
    • Enhui Fu
    • Tianyang Liu
    • Siyang Yu
    • Xiaohang Chen
    • Lianhao Song
    • Huihuang Lou
    • Fen Ma
    • Siwei Zhang
    • Sajjad Hussain
    • Junnan Guo
    • Ji Sun
    • Pingyang Yu
    • Xionghui Mao
    • Lanlan Wei
  • View Affiliations

  • Published online on: May 29, 2020     https://doi.org/10.3892/or.2020.7628
  • Pages: 698-710
  • Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to examine the potential role of human heparin‑binding epidermal growth factor (HB‑EGF) secreted by M2 macrophages in the development of radioresistance in head and neck squamous cell carcinoma (HNSCC). Immunohistochemistry was used to detect radiosensitivity in human papilloma virus (HPV)‑positive and HPV‑negative HNSCC tissues and immunohistochemical staining with specific antibodies for macrophage surface markers was used to assess the infiltration of M1 and M2 macrophages in HPV‑positive and ‑negative HNSCC tissues. The expression of HB‑EGF in HPV‑positive and ‑negative HNSCC tissues was determined by multi‑cytokine detection in order to determine the relationship between HB‑EGF and radiosensitivity. M1 and M2 macrophages were co‑cultured with the HNSCC cell line CAL27 and treated with HB‑EGF and its neutralizing antibodies to assess radiation sensitivity. Finally, the major DNA double‑strand break repair pathways required for the activation of HB‑EGF and promotion of epidermal growth factor receptor (EGFR) were identified. The results revealed that radiosensitivity was higher in HPV‑positive HNSCC compared with HPV‑negative. There was a higher infiltration of M2 macrophages in HPV‑negative HNSCC, which were revealed as the main source of HB‑EGF secretion. Furthermore, it was determined that overexpression of HB‑EGF induced radioresistance in HPV‑negative HNSCC. HB‑EGF promoted the activation of the non‑homologous end‑joining pathway by activating EGFR. To the best of our knowledge, this is the first study to demonstrate the association between HB‑EGF and radiosensitivity in HNSCC. These results indicated that the secretion of HB‑EGF by M2 macrophages could induce radioresistance of HPV‑negative HNSCC.

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August-2020
Volume 44 Issue 2

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

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APA
Fu, E., Liu, T., Yu, S., Chen, X., Song, L., Lou, H. ... Wei, L. (2020). M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF. Oncology Reports, 44, 698-710. https://doi.org/10.3892/or.2020.7628
MLA
Fu, E., Liu, T., Yu, S., Chen, X., Song, L., Lou, H., Ma, F., Zhang, S., Hussain, S., Guo, J., Sun, J., Yu, P., Mao, X., Wei, L."M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF". Oncology Reports 44.2 (2020): 698-710.
Chicago
Fu, E., Liu, T., Yu, S., Chen, X., Song, L., Lou, H., Ma, F., Zhang, S., Hussain, S., Guo, J., Sun, J., Yu, P., Mao, X., Wei, L."M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF". Oncology Reports 44, no. 2 (2020): 698-710. https://doi.org/10.3892/or.2020.7628