Research Papers:
VEGF/pSTAT3 induces differentiation of monocytic MDSCs in oral cancer
Yan-Hong Ni1,*, Liang Ding1,*, Xiao-Feng Huang2, Zhi-Yong Wang2, Sheng Chen2, Yu-Xian Song1, Ying-Chun Dong1, Zi-Chun Hua1, Ya-Yi Hou1 and Qin-Gang Hu2
1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, the State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, P. R. China
2Departments of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School, Nanjing University, Nanjing, P. R. China
*These authors contributed equally to this work
Correspondence to:
Qin-Gang Hu, email: [email protected]
Ya-Yi Hou , email: [email protected]
Keywords: mo-MDSCs; VEGF; OSCC; STAT3; differentiation
Received: October 13, 2016 Accepted: February 27, 2018 Published:
ABSTRACT
Monocytic myeloid-derived suppressor cells (mo-MDSCs) and dendritic cells (DCs) are both derived from monocytes. Moreover, over-expressed vascular endothelial cell growth factor (VEGF) is correlated with decreased DCs numbers in oral squamous cell carcinoma (OSCC). However, the role of VEGF in the differentiation and migration of monocytes in OSCC is unclear. The numbers of monocytes and CD14+HLA-DRlow/–mo-MDSCs were assessed in peripheral blood samples from 330 pre- and post-operative OSCC patients and 60 healthy controls. We found that frequencies of mo-MDSCs were higher in OSCC patients but decreased in postoperative patients. Moreover, the expression of VEGF, CD14, STAT3, and p-STAT3 and correlations of VEGF and STAT3 were determined by immunohistochemical analysis. VEGF expression in stroma positively correlated with STAT3 activation. Furthermore, the role of VEGF in the switch of monocytes into mo-MDSCs or DCs was also determined. VEGF secreted by OSCC cells in vitro decreased the DC markers but increased the frequency of mo-MDSCs, which was constrained by bevacizumab, an anti-VEGF antibody, and the STAT3 inhibitor. The expression of VEGF and activation of STAT3 in OSCC promoted the migration of monocytes. Therefore, VEGF could affect the differentiation and migration of monocytes via STAT3 activation in OSCC.