Regulation of differentiation and growth of normal adult and neoplastic epithelia by inductive mesenchyme

Abstract

Since adult epithelial cells from the urogenital tract are unquestionably capable of expressing alternative phenotypes when induced by embryonic or neonatal mesenchymes, we examined the effect of certain inductive mesenchymes on the differentiation and growth of the DT by growing 0.5 mm3 fragments of the DT in association with mesenchyme from various embryonic and neonatal rat organ rudiments. Whereas grafts of DT alone contained narrow ducts lined with undifferentiated epithelial cells characteristic of the DT, the DT derived epithelium of UGM + DT, SVM + DT or BUG-M + DT recombinations differentiated into tall columnar secretory epithelial cells organized into large cystic ducts. These mesenchyme induced changes in histodifferentiation of the DT cells were coupled to a loss of tumorigenesis since the mesenchyme induced highly differentiated DT cells never formed tumours. This reduction in growth rate and loss in tumorigenesis of mesenchyme induced DT epithelial cells was accompanied by a reduction in [3H]thymidine labelling index and the expression of a secretory phenotype as demonstrated by both light microscopy and electron microscopy. These findings demonstrate that the connective tissue environment can have profound regulative effects on both normal and neoplastic epithelial cells.