Differential growth properties of normal and malignant esophageal epithelial cells: a possible cross talk between transforming growth factor-beta1 and epidermal growth factor signaling.

Comparative cultures of normal and malignant cells are important for understanding the growth properties of tumors. Although many cell lines have been established from esophageal cancers, the growth properties of normal and cancer-derived esophageal epithelial cells have not been compared extensively. We succeeded in establishing an assay system in serum-free conditions for normal human esophageal epithelial cells (HEE cells) and 14 cancer-derived esophageal epithelial cell lines (TE-cell lines). The growth properties of these cells were characterized upon stimulation with various growth-related factors. Among these factors, acidic fibroblast growth factor (aFGF) was the most effective stimulant for both the HEE cells and all the TE-cell lines. Most TE-cell lines required a higher concentration of calcium for their growth than did the HEE cells. Transforming growth factor-beta1 (TGF-beta1) inhibited the growth of HEE cells and 7 TE-cell lines; however, the other 7 TE-cell lines were resistant to the inhibitory effect of TGF-beta1. Interestingly, epidermal growth factor (EGF) had a much greater stimulatory effect on the TGF-beta1-resistant cells than the TGF-beta1-sensitive cells. Although ethanolamine enhanced the growth-promoting ability of EGF or aFGF in the TGF-beta1-sensitive cells, it had no effect on the TGF-beta1-resistant cells. These findings suggested a possible cross talk between TGF-beta1 and EGF signaling, and an important role of ethanolamine in the signaling pathways of growth factors. This serum-free culture system will contribute to clarify the altered signaling pathways of esophageal cancer.