Exploring the effects of hyperglycemic stress in oral squamous cell carcinoma

Abstract

This study delves into the intricate relationship between hyperglycemia, radiation therapy, and

the progression of Oral Squamous Cell Carcinoma (OSCC). Epithelial-Mesenchymal Transition (E

M) emerges as a pivotal factor influencing cancer development, metastasis, and resistance to

radiation. The investigation extends to the intersection of cellular glucose metabolism and

hyperglycemia, emphasizing the comparative analysis of cancer cells in response to ionizing

radiation.

The study subjected OSCC cells to a 7-day regimen of hyperglycemic metabolic stress. By

exploiting stressed OSCC cells, we crafted 3D tumor spheroids and conducted a comprehensive

array of cytological, proteomic, and transcriptomic analyses. The development of an in vitro

model of hyperglycemic stress and the insights gained into the relationship between

hyperglycemia, ionizing radiation, and Epithelial-Mesenchymal Transition (EMT) transcription

markers advance our understanding of OSCC through comprehensive transcriptomic profiling.

Transcription marker analysis through qRT-PCR provided a clear and distinct picture of the

expression pattern in hyperglycemia-stressed BICR22 spheroids post-radiation. Both epithelial

marker (E-CAD) and mesenchymal marker (VIM) were present, accompanied by an increase in

TWIST, an Epithelial-Mesenchymal Transition Transcription Factor (EMT-TF) induced by high

glucose levels. Importantly, our findings demonstrate a substantial increase in the post-radiation

survival rate of BICR22 cell lines under conditions of hyperglycemia, correlating with enhanced

metastatic capacity and resistance to radiation, potentially mediated by the EMT-TF TWIST.

The study provides a better perspective on the complex dynamics at play in OSCC progression

and treatment response, offering valuable insights for future therapeutic interventions and

potentially sheds light on novel therapeutic avenues for oral squamous cell carcinoma,

contributing to the evolving landscape of oral cancer research.