M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation.
M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation.
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DOI：
10.1038/srep27548
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发表时间：
2016-06-08
影响因子：
4.6
通讯作者：
Tohnai I
中科院分区：
文献类型：
--
作者：
Okubo M;Kioi M;Nakashima H;Sugiura K;Mitsudo K;Aoki I;Taniguchi H;Tohnai I
尽管放射是治疗口腔癌患者的标准疗法之一，但即使在疾病的早期阶段，肿瘤也会复发，对预后和生活质量产生负面影响。我们以前发现，CD11b+骨髓源性细胞（BMDC）被招募到人多形性胶质母细胞瘤（GBM）中，导致血管系统重组和肿瘤再生长。然而，目前尚不清楚这些细胞如何促进肿瘤血管形成。在本研究中，我们研究了浸润的CD11b+髓样细胞在口腔鳞状细胞癌（OSCC）血管化和复发中的作用。在异种移植小鼠模型中，局部照射引起肿瘤血管损伤和缺氧，并增加CD11b+骨髓细胞的浸润。这些浸润细胞具有M2巨噬细胞（M2Mφs）的特征，并与促进血管形成有关。与未照射的肿瘤相比，照射后M2Mφs促进肿瘤复发进展。此外，我们发现，CD11b+髓系细胞，以及CD206+ M2Mφs，在放疗后复发的人口腔鳞癌标本中增加。我们的研究结果可能会导致潜在的临床生物标志物或放射性口腔鳞癌患者的治疗目标的发展。
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.