Hypoxia-inducible factor-1α and glucose transporter 1 in the malignant transformation of oral lichen planus

Xia-Xia Wang; Hong-Ying Sun; Qiao-Zhen Yang; Bin Guo; Yin Sai; Jie Zhang

Hypoxia-inducible factor-1α and glucose transporter 1 in the malignant transformation of oral lichen planus

Int J Clin Exp Pathol. 2017 Aug 1;10(8):8369-8376. eCollection 2017.

Authors

Xia-Xia Wang¹, Hong-Ying Sun¹, Qiao-Zhen Yang¹, Bin Guo², Yin Sai², Jie Zhang¹

Affiliations

¹ Department of Stomatology, Huashan Hospital, Fudan University Shanghai, P. R. China.
² School of Life Science, Institute of Genetics Shanghai, P. R. China.

PMID: 31966688
PMCID: PMC6965416

Abstract

Hypoxia-inducible factor-1α (HIF-1α) and glucose transporter 1 (GLUT1) are key factors in numerous physiological and pathological processes. However, studies on their involvement in the pathogenesis of oral lichen planus (OLP) and its progression toward oral squamous cell carcinomas (OSCC) are scarce. In this study, we examined the protein and gene expressions of both HIF-1α and GLUT1 in normal mucosa, nonatrophic OLP (OLPI), atrophic OLP (OLPII), and OSCC resulting from OLP. Tissues were obtained from 60 cases of OLP patients (n=36 for OLPI, n=24 for OLPII), 20 cases of OSCC patients and 30 healthy control individuals. In addition, in order to investigate if the pathological changes are due to hypoxia, we cultured keratinocytes under hypoxia conditions and measured the expression of HIF-1α and GLUT1. The results indicated that the expressions of HIF-1α and GLUT1 were gradually amplified from normal mucosa to OLPI, OLPII, and OSCC. The expression of both HIF-1α and GLUT1 in OLPII was significantly greater than OLPII. Likewise, the HIF-1α and GLUT1 expressions in OSCC were markedly higher compared to both OLPI and OLPII. Similar trends were obtained in real time PCR and Western blot analyses. A progressive increased micro-vessel density (MVD) was also recorded from normal mucosa to OLPI, OLPII, and OSCC. Moreover, the correlation analysis revealed significant positive correlations between HIF-1α and GLUT1 which were both correlated with MVD in the OLP and OSCC groups. Culture of keratinocytes isolated from OLP tissues under hypoxic and normoxic conditions showed a time-dependent inhibition of keratinocyte proliferation and increased expression of HIF-1α and GLUT1 under hypoxia conditions. In summary, we provided new evidence that hypoxia markers HIF-1α and GLUT1 are upregulated in OLP and are potentially involved in pathological changes leading to malignant transformation of OLP. Further characterization of these factors will provide new ideas for the diagnosis and treatment of OLP.

Keywords: GLUT1; HIF-1α; Oral lichen planus; hypoxia; malignant transformation; oral squamous cell carcinomas.