TY - JOUR
T1 - Effect of transforming growth factor-beta on plasminogen activator production of cultured human uveal melanoma cells
AU - Park, Susanna S.
AU - Li, Ling
AU - Korn, Tommy S.
AU - Mitra, Monalisa M.
AU - Niederkorn, Jerry Y.
N1 - Funding Information:
Thi\ work wab supported by a Research to Prevent Blindness c'ari'csr Development Award (SSP).
PY - 1996
Y1 - 1996
N2 - Purpose. Human uveal melanoma cells have been shown to produce plasminogen activator (PA), an enzyme which can enhance tumor metastasis by promoting degradation of extracellular matrix. This study used cultured human uveal melanoma cells to determine whether the PA production of uveal melanoma cells could be modulated by transforming growth factor-beta2 (TGF-beta2), a mitogen present in the uvea. Methods. Five different cell lines of human uveal melanoma of differing cellular morphology (2 spindle, 2 epithelioid, 1 mixed) derived from tumors from different locations in the eye (3 choroidal, 1 ciliochoroidal, 1 orbital) were grown in serum free media, in the presence or absence of TGF-beta2 (1 ng/ml to 100 ng/ml). After 24 hrs, the conditioned media were collected and quantitated for PA activity by measuring the radial diffusion in fibrin-agarose clot and for total PA concentration using an enzyme-linked immunoassay. Results. Among the cell lines studied, all produced PA. Cell lines derived from intraocular tumors secreted tissue-type PA (tPA), and TGF-beta2 stimulated tPA activity and secretion of cell lines containing epithelioid cells but had no effect on spindle cells. In contrast, tumor cells isolated from an orbital tumor secreted urokinase (uPA), activity and secretion of which was inhibited by TGF-beta2. Conclusions. We conclude that cultured human uveal melanoma cells produce either tPA or uPA, and TGF-beta2 can have a variable effect on PA production of these cells.
AB - Purpose. Human uveal melanoma cells have been shown to produce plasminogen activator (PA), an enzyme which can enhance tumor metastasis by promoting degradation of extracellular matrix. This study used cultured human uveal melanoma cells to determine whether the PA production of uveal melanoma cells could be modulated by transforming growth factor-beta2 (TGF-beta2), a mitogen present in the uvea. Methods. Five different cell lines of human uveal melanoma of differing cellular morphology (2 spindle, 2 epithelioid, 1 mixed) derived from tumors from different locations in the eye (3 choroidal, 1 ciliochoroidal, 1 orbital) were grown in serum free media, in the presence or absence of TGF-beta2 (1 ng/ml to 100 ng/ml). After 24 hrs, the conditioned media were collected and quantitated for PA activity by measuring the radial diffusion in fibrin-agarose clot and for total PA concentration using an enzyme-linked immunoassay. Results. Among the cell lines studied, all produced PA. Cell lines derived from intraocular tumors secreted tissue-type PA (tPA), and TGF-beta2 stimulated tPA activity and secretion of cell lines containing epithelioid cells but had no effect on spindle cells. In contrast, tumor cells isolated from an orbital tumor secreted urokinase (uPA), activity and secretion of which was inhibited by TGF-beta2. Conclusions. We conclude that cultured human uveal melanoma cells produce either tPA or uPA, and TGF-beta2 can have a variable effect on PA production of these cells.
KW - Growth factors
KW - Human
KW - Melanoma
KW - Plasminogen activator
KW - Transforming growth factor-beta
KW - Urokinase
KW - Uveal
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U2 - 10.3109/02713689609003459
DO - 10.3109/02713689609003459
M3 - Article
C2 - 8670784
AN - SCOPUS:0029738055
SN - 0271-3683
VL - 15
SP - 755
EP - 763
JO - Current Eye Research
JF - Current Eye Research
IS - 7
ER -