M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HBEGF.
Oncol Rep
; 44(2): 698-710, 2020 08.
Article
in En
| MEDLINE
| ID: mdl-32627036
ABSTRACT
The aim of the present study was to examine the potential role of human heparinbinding epidermal growth factor (HBEGF) 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 HPVnegative HNSCC tissues and immunohistochemical staining with specific antibodies for macrophage surface markers was used to assess the infiltration of M1 and M2 macrophages in HPVpositive and negative HNSCC tissues. The expression of HBEGF in HPVpositive and negative HNSCC tissues was determined by multicytokine detection in order to determine the relationship between HBEGF and radiosensitivity. M1 and M2 macrophages were cocultured with the HNSCC cell line CAL27 and treated with HBEGF and its neutralizing antibodies to assess radiation sensitivity. Finally, the major DNA doublestrand break repair pathways required for the activation of HBEGF and promotion of epidermal growth factor receptor (EGFR) were identified. The results revealed that radiosensitivity was higher in HPVpositive HNSCC compared with HPVnegative. There was a higher infiltration of M2 macrophages in HPVnegative HNSCC, which were revealed as the main source of HBEGF secretion. Furthermore, it was determined that overexpression of HBEGF induced radioresistance in HPVnegative HNSCC. HBEGF promoted the activation of the nonhomologous endjoining pathway by activating EGFR. To the best of our knowledge, this is the first study to demonstrate the association between HBEGF and radiosensitivity in HNSCC. These results indicated that the secretion of HBEGF by M2 macrophages could induce radioresistance of HPVnegative HNSCC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Radiation Tolerance
/
Papillomavirus Infections
/
Heparin-binding EGF-like Growth Factor
/
Squamous Cell Carcinoma of Head and Neck
/
Head and Neck Neoplasms
/
Macrophages
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2020
Document type:
Article