Abstract
Purpose :
Matrix metalloproteinase (MMP)-8 is the most potent MMP for degrading collagen type-1 and plays an important role in inflammatory reactions and tissue remodeling processes. MMP-8 is expressed primarily by polymorphonuclear leukocytes (PMN) and has not been reported to be expressed constitutively by most non-PMN cells. We tested the hypothesis that cultured human uveal melanocytes and uveal melanoma cells express MMP-8 constitutively.
Methods :
Early passages of cultured human uveal melanocytes, uveal melanoma cells and other cell types were seeded into 12-well plates with containing culture media supplemented with 10% serum and cultured for 24 hours. The culture media was then replaced with culture media with 1% serum for an additional 24 hours before conditioned media collected. MMP-8 protein levels of the media were measured using an human MMP-8 ELISA kit (R & D System).
Results :
Very high levels of MMP-8 protein were detected in the conditioned media in ten primary cultures of uveal melanocytes (1240 ± 404 pg/ml, mean ± SD) and three uveal melanoma cell lines (2527 ± 2180 pg/ml). It was not detected or only at very low levels (nearly minimum detectable levels) in media from other ocular cells (human retinal pigment epithelial cells, cornea epithelial cells and scleral fibroblasts) and 12 malignant cell lines from other tissues (prostate, ovary, lung, breast, cervical and colon cancers, osteosarcoma and glioblastoma); High levels of MMP-8 were also detected in two cell lines of human cutaneous melanoma cells (1738-2645 pg/ml).
Conclusions :
This is the first report of the expression and secretion of MMP-8 by uveal melanocytes and melanoma cells. The data suggest that uveal melanocytes may play a role in the remodeling process and pathogenesis of inflammatory diseases in the eye via the secretion of MMP-8.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.