Heparin-Binding (Fibroblast) Growth Factors are Potential Autocrine Regulators of Esophageal Epithelial Cell Proliferation

Abstract

We previously established a serum-free culture system for normal human esophageal epithelial cells [1, 2] and reported that crude bovine neural tissue extracts were an effective growth stimulant of normal human esophageal epithelial cells. Neural extracts are a widely used source of heparin-binding (fibroblast) growth factors (HBGF) [3]. Esophageal cell lines also respond to and express epidermal growth factor (EGF) and transforming growth factor (TGF-α) [4]. These results prompted us to establish and examine the role of both the EGF and HBGF families in nonmalignant and malignant esophageal epithelial cell lines. The same culture system used for normal human esophageal cell culture was applied to establish an immortal nonmalignant epithelial cell line from normal esophageal epithelium from the BALB/c mouse (MEE). In the absence of neural extract, a malignant cloned cell line (MEE/C8) was selected from the MEE cells. Here, we compare the growth kinetics of MEE, MEE/C8, and cell lines derived from human esophageal cancer, and their response to EGF and HBGF-1 (acidic fibroblast growth factor, FGF). We show that an HBGF-like activity may play a growth cycle-dependent autocrine role in nonmalignant esophageal epithelial cell proliferation and a constitutive role in support of the malignant cell line.