M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation.
Despite the fact that radiation is one of the standard therapies in the treatment of patients with oral cancer, tumours can recur even in the early stages of the disease, negatively impacting prognosis and quality of life. We previously found that CD11b(+) bone marrow-derived cells (BMDCs) were recruited into human glioblastoma multiforme (GBM), leading to re-organization of the vasculature and tumour regrowth. However, it is not yet known how these cells contribute to tumour vascularization. In the present study, we investigated the role of infiltrating CD11b(+) myeloid cells in the vascularization and recurrence of oral squamous cell carcinoma (OSCC). In a xenograft mouse model, local irradiation caused vascular damage and hypoxia in the tumour and increased infiltration of CD11b(+) myeloid cells. These infiltrating cells showed characteristics of M2 macrophages (M2Mφs) and are associated with the promotion of vascularization. M2Mφs promoted tumour progression in recurrence after irradiation compared to non-irradiated tumours. In addition, we found that CD11b(+) myeloid cells, as well as CD206(+) M2Mφs, are increased during recurrence after radiotherapy in human OSCC specimens. Our findings may lead to the development of potential clinical biomarkers or treatment targets in irradiated OSCC patients.
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Makiko
M
Okubo
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Mitomu
M
Kioi
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Hideyuki
H
Nakashima
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Kei
K
Sugiura
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Kenji
K
Mitsudo
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Ichiro
I
Aoki
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Hideki
H
Taniguchi
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Iwai
I
Tohnai
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D039481:CD11b Antigen / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000528:radiation effects; D045744:Cell Line, Tumor; D006801:Humans; D008264:Macrophages / Q000473:pathology; D051379:Mice; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D022423:Myeloid Cells / Q000473:pathology / Q000528:radiation effects; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D012008:Recurrence; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D039481:CD11b Antigen; C509295:ITGAM protein, human