Local environmental influences on uveal melanoma

Abstract

BACKGROUNDUveal melanomas of the choroid and ciliary body are aggressive tumors causing the death of approximately 50% of patients. In contrast, iris melanomas only infrequently metastasize; why these differences exist is not known. The local environment can regulate cancer growth and development, and it is probable the aqueous and vitreous humors have an important role in regulating uveal melanoma behavior.METHODSTo explore this possibility cultures of uveal melanoma were exposed to aqueous and vitreous and the effects investigated using invasion and proliferation assays. ChemiArrays (Chemicon International, Temecula, Calif) were performed to determine which regulatory factors might influence the process.RESULTSThe vitreous universally promoted uveal melanoma invasion, whereas the aqueous mainly had no effect or was inhibitory. Tumor location, and the baseline invasion of the melanoma, affected the ability of aqueous and vitreous from different patients to regulate invasive behavior. Proliferation was not significantly altered as a result of exposure to the aqueous or vitreous. The ability of the humors to regulate uveal melanomas may involve TIMP‐2, TIMP‐3, and TGF‐β2, as high expression was found by ChemiArray analysis and there were differences in the levels of the regulators in the aqueous compared with the vitreous.CONCLUSIONSThe findings suggest that in situ uveal melanoma development reflects an interaction between the tumor and the environment of the eye. Exposure to the aqueous would therefore contribute to the benign nature of iris melanomas, whereas potential interaction with the vitreous appears to promote the aggressive behavior of posterior uveal melanomas. Cancer 2008. © 2008 American Cancer Society.

Investigating Vitreous Cytokines in Choroidal Melanoma

“…These biological processes are mediated by interactions among various cellular and soluble components of the TME, ultimately leading to either a pro-tumorigenic (growth and spread) or anti-tumorigenic (regression) outcome in UM [3,[21][22][23][24][25][26]. Given the growing interest in using less invasive and more advantageous liquid biopsy-based approaches to study and manage solid cancers, the protein markers (including inflammatory mediators and angiogenic factors) have also been increasingly investigated in ocular fluids of UM-affected eyes in recent years [3,4,20,25,26,[32][33][34][35][36][37][38][39]. While both aqueous and vitreous humor have been used for this purpose (obtained in vivo or ex vivo from the eyes undergoing eye-preserving therapy or enucleation surgery), the data on vitreous remain limited due to fewer studies that focused on this ocular fluid by statistically analyzing either a selected set of cytokines (<30 analytes) [3,25,26] or a small discovery cohort (<10 UM samples) for a large number of proteins [20].…”

Establishment and molecular characterisation of seven novel soft-tissue sarcoma cell lines

“…Cells were seeded at a density of 2 × 10 3 in individual wells of a 96-well plate and the MTT ((4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay was performed as described previously (Canovas et al , 2008). The ratio of absorbance in the test wells to control wells (containing 100  μ l DMSO only) was calculated as relative MTT activity and used as a surrogate for the number of viable cells remaining in culture.…”