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Expression of Angiogenic Factors Cyr61 and Tissue Factor in Uveal Melanoma
Teresa M. Walker, PhD;
Paul R. van Ginkel, PhD;
Ricardo L. Gee, BS;
Hoda Ahmadi, BS;
Lalita Subramanian, MS;
Bruce R. Ksander, PhD;
Lorraine F. Meisner, PhD;
Daniel M. Albert, MD;
Arthur S. Polans, PhD
Arch Ophthalmol. 2002;120:1719-1725.
Objective To study the expression of angiogenic factors Cyr61 and tissue factor (TF) in uveal melanoma and its correlation with blood vessel density.
Methods Suppression subtractive hybridization was used to identify genes that are differentially expressed between cell lines of uveal melanoma and normal uveal melanocytes. Expression of these genes was subsequently verified in primary uveal melanomas and correlated with the number of blood vessels in archival specimens by immunohistochemical analysis.
Results Cyr61 and TF are expressed at elevated levels in cell lines of uveal melanoma compared with normal uveal melanocytes. Duplication of a region of chromosome arm 1p, encompassing the genes encoding Cyr61 and TF, was observed in the melanoma cell line used in the initial subtractive hybridization. Both genes are also expressed in primary uveal melanomas, and a correlation was found between expression of TF and the number of blood vessels in archival specimens.
Conclusions Cyr61 and TF may contribute to the angiogenic phenotype associated with uveal melanoma. A region of chromosome arm 1p also may contain oncogenes or tumor suppressor genes pertinent to the origins of this type of ocular tumor.
Clinical Relevance New immunotherapies have been devised for the treatment of cancer based on the expression of TF. Similar approaches may be effective in treating uveal melanoma.
From the Departments of Ophthalmology and Visual Sciences (Drs Walker, van Ginkel, Albert, and Polans; Mr Gee; and Mss Ahmadi and Subramanian), Biomolecular Chemistry (Ms Subramanian and Dr Polans), and Population Health Sciences and the State Hygiene Laboratory (Dr Meisner), University of Wisconsin Medical School, Madison; and the Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Mass (Dr Ksander).
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