TGFβ1 and HGF protein secretion by esophageal squamous epithelial cells and stromal fibroblasts in oesophageal carcinogenesis

Abstract

Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) affect tumorigenesis by creating an environment primed for growth and invasion through the secretion of factors, including hepatocyte growth factor (HGF) and transforming growth factor β1 (TGFβ1). In the present study, the levels of α‑smooth muscle actin (α‑SMA), TGFβ1 and HGF were determined immunohistochemically in oesophageal precancerous lesions (low‑ and high‑grade intraepithelial neoplasia; LGIEN and HGIEN, respectively), carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Immunoreactivity was observed in the cytoplasm of oesophageal epithelial cells and stromal fibroblasts. Expression levels of α‑SMA, TGFβ1 and HGF increased significantly in the following order: normal, LGIEN, HGIEN, CIS and SCC. In addition, linear correlations between the expression of α‑SMA, TGFβ1 and HGF and different lesions were observed. Microvessel density (MVD) was measured in all specimens and increased gradually in the normal, LGIEN, HGIEN, CIS and SCC specimens, successively. A linear correlation between MVD and pathological grade was also observed and the MVD in α‑SMA‑, HGF‑ and TGFβ1‑positive groups was higher when compared with that of their negative counterparts. The results of the present study indicated that the frequent overexpression of TGFβ1 and HGF proteins, secreted by oesophageal epithelium and stromal fibroblasts, promoted the progression of oesophageal precancerous lesions via the proliferation of epithelial cells and angiogenesis, through the upregulation of vascular endothelial growth factor (VEGF) expression.