CD98hc has a pivotal role in maintaining the immuno-barrier integrity of basal layer cells in esophageal epithelium

Objectives: The current study aims to find the linker between esophageal epithelial carcinogenesis and chronic inflammation and the origin of hyperproliferative cells in precancerous lesions of esophageal squamous cell carcinoma (ESCC).

Materials and methods: Twenty one normal esophageal tissues from cadavers and 180 paired tissues from 60 surgical resected ESCC specimens were utilized for immunohistochemistry staining against CK14, CK6, CD98hc and Ki67. NE6 cell line was treated with H₂O₂ to mimic chronic inflammation microenvironment and TPA for malignant orientated transformation. Cell proliferation and CD98hc mRNA were assessed by CCK8 assay and RT-qPCR.

Results: CD98hc expression was correlated with chronic inflammation severity, precancerous lesion stage, and epithelial cell proliferative activity. CD98hc expression and proliferation rate of NE6 were up regulated by low dose H₂O₂ treatment and long term TPA treatment. The proliferating cells in hyperplastic and dysplastic tissues could be divided into two patterns by the expression of CK14, CD98hc, CK6 and Ki67: CK14⁺CD98hc⁺CK6^-Ki67^- in basal cells with CK14^-CD98hc^-CK6⁺Ki67⁺ in proliferating cells and CK14⁺CD98hc⁺CK6⁺Ki67⁺ in both basal cells and proliferating cells.

Conclusions: Our study revealed that CD98hc was a marker of cells originated from basal cell in esophagus, ectopic expression of CD98hc in hyperplastic/dysplastic cells by chronic inflammation stimulation crippled the linkage between basal cell and basement membrane, sabotaged the integrity of the barrier in between lamina propria and epithelium, subsequentially initiate carcinogenesis.