Bone morphogenetic protein 7 inhibits tumor growth of human uveal melanoma in vivo.
OBJECTIVE
Bone morphogenetic protein-7 (BMP7), a member of the TGF-beta 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.
Notting
Irene
I
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Buijs
Jeroen
J
Mintardjo
Ratna
R
van der Horst
Geertje
G
Vukicevic
Slobodan
S
Lowik
Clemens
C
Schalij-Delfos
Nicoline
N
Keunen
Jan
J
van der Pluijm
Gabri
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000867:Anterior Chamber / Q000473:pathology; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger