Abstract
Purpose: :
To evaluate the expression of matrix metalloproteinase (MMP)-2,-9,-14 and tissue inhibitor of metalloproteinase (TIMP)-1,-2 in retinoblastoma and to elucidate their roles in the proliferation or differentiation of retinoblastoma cells
Methods: :
Y79, SNUOT-Rb1 or-Rb4 retinoblastoma cells were injected into the intravitreal cavity of nude mice, and enucleation was performed 4weeks later. Immunohistochemistry for MMP-2, 9, 14 and TIMP-1, 2 was performed, which were merged with Ki67, nm23 or TUNEL. With treatment of retinoic acid or bFGF, MMP-2, 9, 14 and TIMP-1, 2 expression in retinoblastoma cells were mesured by western blotting. The effect of a MMP inhibitor on the differentiation or proliferation was evaluated as well.
Results: :
In animal model of retinoblastoma with Y79, SNUOT-RB1, and Rb-4, MMP-2 &-9 were highly expressed in the proliferative area of retinoblastoma, whereas MMP-14 expression was prominent in the differentiated area. With the proliferation of retinoblastoma cells, MMP-2 & -9 expression was increased which were inhibited by a MMP inhibitor. However, with the differentiation of retinoblastoma cells, MMP-14 expression was increased.
Conclusions: :
Our data suggest that differential expression of MMP-2,-9, or -14 may be a related to proliferation or differentiation of retinoblastoma cells. In addition, MMP inhibitor could be applied as a treatment agent for retinoblastoma.
Keywords: retinoblastoma • immunohistochemistry • tumors