Implication of stem cell factor in the proliferation of choroidal melanocytes

The tyrosine kinase receptor c-kit and its ligand stem cell factor exert a broad range of biological activities during organogenesis. It also improves normal cell development including complex biological responses involved in the differentiation and proliferation of the melanocytes. Diffuse uveal me lanocytic proliferation is a rare paraneoplasic syndrome, resulting in rapi d bilateral visual loss due to proliferation of melanocytes within the chor oid, We have therefore investigated whether the c-kit/stem cell factor path way regulates the proliferation of choroidal melanocytes and also if such p athway plays a role in bilateral uveal melanocytic proliferation. Normal cu ltured melanocytes of the choroid and paraffin-embedded sections of melanoc ytic proliferation were studied. C-kit expression and effects of stem cell factor were measured. Western blot assays of cell extracts demonstrated tha t c-kit was expressed in choroidal melanocytes. Immunocytochemical analysis on cultured melanocytes showed a cytoplasmic distribution. Immunohistochem ical analysis on melanocytic proliferation showed a strong cytoplasmic dist ribution in the pigmented spindle-shaped melanocytes localized in the multi ple focal areas of choroidal thickening. The addition of stem cell factor d id not change melanocyte morphologies and was mitogenic in the presence of bFGF, isobutyl-l-methylxanthine and cholera toxin. In contrast, stem cell f actor was not able to produce any significant melanin. Activation of c-kit by its ligand may contribute to the proliferation of choroidal melanocytes. (C) 2001 Academic Press.