Local environmental influences on uveal melanoma: vitreous humor promotes uveal melanoma invasion, whereas the aqueous can be inhibitory.
BACKGROUND
Uveal 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.


METHODS
To 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.


RESULTS
The 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-beta2, 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.


CONCLUSIONS
The 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.
Canovas
David
D
Academic Unit of Ophthalmology and Orthoptics, Section of Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom.
Rennie
Ian G
IG
Nichols
Carmel E
CE
Sisley
Karen
K
D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001082:Aqueous Humor / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002633:Chemotaxis / Q000502:physiology; D002830:Choroid Neoplasms / Q000473:pathology; D002924:Ciliary Body / Q000473:pathology; D016207:Cytokines / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015811:Iris Neoplasms / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D046509:Tissue Culture Techniques; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000187:drug effects; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000187:drug effects; D053781:Transforming Growth Factor beta2 / Q000187:drug effects; D014604:Uveal Neoplasms / Q000473:pathology*; D014822:Vitreous Body / Q000503:physiopathology*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D016207:Cytokines; D019717:Tissue Inhibitor of Metalloproteinase-3; D053781:Transforming Growth Factor beta2; D019716:Tissue Inhibitor of Metalloproteinase-2