Effects of medium conditioned by retinal pigmented epithelial cells on neurotransmitter phenotype in retinoblastoma cells.

We previously reported that medium conditioned by retinal pigmented epithelial cells can induce cellular differentiation in human retinoblastoma cells. Extensive neurite outgrowth, increased expression of neuronal marker molecules and decreases expression of glial marker molecules are characteristic of the differentiated phenotype. In the studies described here, we examine whether modulations in the expression of potential neurotransmitter molecules, catecholamines and indolealkyl amines, might be associated with the differentiation of retinoblastoma cells. Concentrations of serotonin, 5-hydroxyindoleacetic acid, 3-methoxytyrosine, homovanillic acid, and 3-methoxy-4-hydroxyphenylacetic acid in extracts of differentiated and undifferentiated retinoblastoma cells were assessed by HPLC. The results show that serotonin and its metabolite, 5-hydroxyindoleacetic acid, are characteristically present in undifferentiated cells. Dopa metabolites, 3-methoxytyrosine, homovanillic acid and 3-methoxy-4-hydroxy-phenylacetic acid, are uniquely present in differentiated cells. It appears that differentiation of retinoblastoma cells induced by factors secreted by retinal pigmented epithelial cells involves a switch from a serotonergic phenotype to one dominated by metabolites of dopa. These findings may provide clues about the factors that control retinoblastoma cells and metastasis.