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Differential Roles of Matrix Metalloproteinase-9 and-2, Depending on Proliferation or Differentiation of Retinoblastoma Cells

Cited 22 time in Web of Science Cited 22 time in Scopus
Issue Date
2010-03
Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Citation
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE; Vol.51 3; 1783-1788
Abstract
PURPOSE. To investigate the differential roles of matrix metalloproteinase (MMP)-9 and MMP-2 in the proliferation or differentiation of retinoblastoma cells. METHODS. Cell proliferation assay with an MMP-9 inhibitor and cell viability assay with an MMP-2 inhibitor were performed in retinoblastoma cells with 5 ng/mL fibroblast growth factor 2 for proliferation, 0.1% bovine serum albumin for differentiation, or reverse transcriptase-polymerase chain reaction (RTPCR) for MMP-9, MMP-2, and their tissue inhibitors TIMP-1 and TIMP-2. Immunohistochemistry for MMP-2 and nm23 was performed using an experimental model of retinoblastoma. With the use of an MMP-2 inhibitor, Western blot analysis was performed for neurofilament, extracellular signal-regulated kinases 1 and 2 (ERK 1/2), and phospho-ERK 1/2, and neurite length was measured in differentiated retinoblastoma cells. RESULTS. With the proliferation of retinoblastoma cells, MMP-9 expression was upregulated without alteration of MMP-2, TIMP-1, or TIMP-2. However, proliferation was not affected by the inhibition of MMP-9 activity. Interestingly, only MMP-2 expression, colocalized with differentiated cells in retinoblastoma tissue, was significantly increased in the differentiation of retinoblastoma cells. Inhibition of MMP-2 activity did not affect cellular viability but attenuated neurite outgrowth and neurofilament expression of differentiated retinoblastoma cells, which was mediated through the suppression of ERK 1/2 activation. CONCLUSIONS. The authors suggest that differential expression of MMP-9 and -2 could reflect biological features, such as proliferation and differentiation, of retinoblastoma cells. In particular, MMP-2 could be directly involved in the regulation of differentiation of retinoblastoma cells. Therefore, therapeutic targeting to MMP-2 may prove useful for reducing malignancy through the differentiation of retinoblastoma cells. (In-vest Ophthalmol Vis Sci. 2010;51:1783-1788) DOI:10.1167/iovs.09-3990
ISSN
0146-0404
Language
English
URI
https://hdl.handle.net/10371/77889
DOI
https://doi.org/10.1167/iovs.09-3990
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College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
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