IOVS Journal of Clinical Microbiology
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(Investigative Ophthalmology and Visual Science. 2007;48:4882-4889.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0505
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Bone Morphogenetic Protein 7 Inhibits Tumor Growth of Human Uveal Melanoma In Vivo

Irene Notting,1 Jeroen Buijs,2 Ratna Mintardjo,1 Geertje van der Horst,2 Slobodan Vukicevic,3 Clemens Lowik,4 Nicoline Schalij-Delfos,1 Jan Keunen,5 and Gabri van der Pluijm2,4

1From the Departments of Ophthalmology, 2Urology, 4Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; the 3Department of Anatomy, School of Medicine, Zagreb, Croatia; and the 5Institute of Ophthalmology, Nijmegen University Medical Center, Nijmegen, The Netherlands.

PURPOSE. Bone morphogenetic protein-7 (BMP7), a member of the TGF-ß superfamily, is essential for early ocular morphogenesis, and lack of BMP7 causes epithelial development disturbances in the eye. In the present study, the association of tumorigenicity and malignant behavior of human uveal melanoma with BMP7 expression and the possibility that overexpression of BMP7 in uveal melanoma affects intraocular tumor growth in vivo were investigated.

METHODS. To establish the role of BMP7 in uveal melanoma progression, the human OCM-1 cell line was stably transfected to overexpress BMP7 (OCM-1 FRT/BMP7) using targeted homologous recombination.

RESULTS. Transcriptional profiling revealed low or no detectable expression of BMP7 in primary tumor tissue of patients with uveal melanoma. In line with these clinical observations, BMP7 mRNA levels were low or not detectable in cultured human uveal melanoma cell lines, when compared with normal cultured melanocytes. Inoculation of OCM-1 FRT/BMP7 cells into the anterior chamber of the eye of nude mice inhibited tumor progression significantly, compared with progression in the control cell line (no BMP7 expression).

CONCLUSIONS. Collectively, the data provide novel evidence that decreased BMP7 expression contributes to progression of uveal melanoma. Furthermore, BMP7 may represent a novel therapeutic molecule for repression of tumor growth in uveal melanoma.




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