Implication of stem cell factor in the proliferation of choroidal melanocytes.

ABSTRACT

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 melanocytic proliferation is a rare paraneoplasic syndrome, resulting in rapid bilateral visual loss due to proliferation of melanocytes within the choroid. We have therefore investigated whether the c-kit/stem cell factor pathway regulates the proliferation of choroidal melanocytes and also if such pathway plays a role in bilateral uveal melanocytic proliferation. Normal cultured melanocytes of the choroid and paraffin-embedded sections of melanocytic proliferation were studied. C-kit expression and effects of stem cell factor were measured. Western blot assays of cell extracts demonstrated that c-kit was expressed in choroidal melanocytes. Immunocytochemical analysis on cultured melanocytes showed a cytoplasmic distribution. Immunohistochemical analysis on melanocytic proliferation showed a strong cytoplasmic distribution in the pigmented spindle-shaped melanocytes localized in the multiple focal areas of choroidal thickening. The addition of stem cell factor did not change melanocyte morphologies and was mitogenic in the presence of bFGF, isobutyl-1-methylxanthine and cholera toxin. In contrast, stem cell factor was not able to produce any significant melanin. Activation of c-kit by its ligand may contribute to the proliferation of choroidal melanocytes.