The effect of epidermal growth factor and transforming growth factor β₁ on proliferation and differentiation of urothelial cells in urinary bladder explant culture

Abstract

The effects of two growth factors, EGF and TGF beta 1, on growth and differentiation of different populations of urothelial cells in explant cultures of mouse urinary bladder have been studied by electron microscopy and lectin analysis. In an explant culture 10 days after the implantation three different populations of urothelial cells can be distinguished. Original urothelial cells, which are integral part of the explant, new urothelial cells, which cover the baso-lateral sides of the explant and are organized in a multilayer epithelium, and new urothelial cells, which are not any more in direct contact with the explant and grow over the membrane in epithelium-like structure. Exogenously added EGF or TGF beta 1 did not affect either the formation or the thickness of multilayered urothelium, so cells were proliferating on the free surfaces of stroma as well as on the epithelium expanding over the membrane. In the absence of growth factors in medium, the newly formed baso-lateral multilayered epithelium bordering the stroma shows ultrastructural signs of terminal differentiation suggesting that for cell proliferation and differentiation the action of stroma is of crucial importance. On the other hand, the differentiation of the epithelium spreading over the membrane, but not its thickness, is affected by exogenously added TGF beta 1. Solely in TGF beta 1-treated cultures a differentiation similar to that in vivo takes place. The apoptosis of the urothelial cells was not increased by TGF beta 1. The lectin analysis by WGA and ConA conjugated with ferritin revealed that ConA-ferritin combines only with the surface cells which grow over the membrane in the absence of TGF beta 1.

Epidermal Growth Factor Protects Epithelial Cells against Fas-induced Apoptosis

“…Many breast cancer cells express multiple members of the ErbB family including ErbB1 (EGF receptor) and ErbB2 (Neu) (1,6). In addition, many breast cancers also express either EGF or transforming growth factor ␣ and are thus able to activate EGF receptors in the tumor cells via autocrine and paracrine mechanisms (41). The stimulation of the Akt-signaling pathway in breast tumors would also be predicted to provide a survival function during the transformation process.…”

The effects of meglumine gamma linolenic acid (MeGLA) on an organ culture model of superficial bladder cancer

“…Stranded processes between the tumour cells and urothelium suggested that junctional bonding had occurred. Previous studies using SEM have shown similar images of the normal and hyperplastic surface [11,21]. BrDU staining is an established method to demonstrate DNA replication [9].…”

“…The experiments with MeGLA on the explant per se further showed that the urothelial surface is able to withstand a toxic insult without denudation of the epithelial surface. The characteristics of these explants are similar to those described previously [17] with a similar division of the explant into normal surface urothelium and epithelial-like growth on the surrounding base [21]. The behaviour, conditions for culture and morphology of these explant systems are, therefore, well established.…”