NOVEL MADIN-DABBY CANINE KIDNEY-CELL CLONES EXHIBIT UNIQUE PHENOTYPESIN RESPONSE TO MORPHOGENS

Novel Madin Darby Canine Kidney cell clones were isolated. These cell clones exhibit differential responsiveness to inducers of tubule or cy st formation in collagen gel culture: hepatocyte growth factor or indu cers of intracellular cAMP formation, respectively. In gel culture, cl one OR93.22.D6 forms cysts and responds with morphological transformat ion to both hepatocyte growth factor and prostaglandin E(1), and is mo st typical of a previously described cell type except for its higher t ransepithelial electrical resistance. OR55.25.II20 forms tubules in cu lture, is unresponsive to hepatocyte growth factor, and forms prostagl andin-induced spherical cysts. OR55.28.V2 forms dense cell spheres und er control conditions, is induced to form tubules by hepatocyte growth factor, and is unresponsive to prostaglandin. OR55.29 forms only cyst s, and is the only clone to form domes in monolayer culture. Tubule fo rmation induced by hepatocyte growth factor, in all clones except OR55 .25.II20, is blocked by a neutralizing antibody. In defined medium, wi thout hepatocyte growth factor or prostaglandin, OR55.25.II20 forms sp ontaneous tubules. This finding indicates that a tubulogenic serum fac tor is not responsible for the observed phenotype. Increasing prostagl andin concentrations lead to inhibition of tubule formation and increa sed cyst formation. This observation suggests that induction of intrac ellular cAMP formation negatively regulates tubule formation in these cells, and implies that cystogenesis may represent a ''default pathway '' for impaired tubulogenesis. These observations demonstrate that som e facets of renal tubulogenesis may be independent of hepatocyte growt h factor, and that care must be exercised when comparing biological st udies utilizing different clones.