CCK expression in enteroendocrine cell is regulated by soluble factor(s) from underlying fibroblasts

Studies on the cross-talk between the intestinal epithelium and the underly ing connective tissue have concentrated on enterocytes. In contrast, little is known about the interactions between the mesenchymal compartment and th e enteroendocrine cells, scattered among the other cell types of the epithe lium. To address this question, a panel of coculture systems between the en teroendocrine STC-1 cell line and three intestinal myofibroblastic cell lin es (MIC) was used in order to assess different levels of regulation, namely cell-cell and cell-matrix interactions, and the role of diffusible factors . We demonstrate that the expression of cholecystokinin, a typical intestin al hormone produced by STC-1 cells, is up-regulated in the presence of a fi broblastic environment through a paracrine pathway involving FGF2. Concomit antly, STC-1 cell morphology and proliferation were also modulated, but thr ough distinct mechanisms according to the origin of fibroblasts. The result s reveal definite epithelio-mesenchymal interactions that may be critical f or the maintenance of phenotype and function of enteroendocrine cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.