基质金属蛋白酶-9 和 -2 根据视网膜母细胞瘤细胞的增殖或分化而发挥不同作用。
Differential roles of matrix metalloproteinase-9 and -2, depending on proliferation or differentiation of retinoblastoma cells.
机构信息
Fight Against Angiogenesis-Related Blindness Laboratory, Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Korea.
出版信息
Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1783-8. doi: 10.1167/iovs.09-3990. Epub 2009 Nov 20.
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 (RT-PCR) 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.
目的
研究基质金属蛋白酶（MMP）-9 和 MMP-2 在视网膜母细胞瘤细胞增殖或分化中的差异作用。
方法
用 MMP-9 抑制剂进行细胞增殖测定，用 MMP-2 抑制剂进行细胞活力测定，在有 5ng/ml 成纤维细胞生长因子 2 促进增殖、0.1%牛血清白蛋白促进分化的视网膜母细胞瘤细胞中进行，或进行逆转录-聚合酶链反应（RT-PCR）检测 MMP-9、MMP-2 及其组织抑制剂 TIMP-1 和 TIMP-2。用视网膜母细胞瘤的实验模型进行 MMP-2 和 nm23 的免疫组化。用 MMP-2 抑制剂，对分化的视网膜母细胞瘤细胞进行神经丝、细胞外信号调节激酶 1 和 2（ERK1/2）和磷酸化 ERK1/2 的 Western blot 分析，并测量神经突长度。
结果
随着视网膜母细胞瘤细胞的增殖，MMP-9 的表达上调，而 MMP-2、TIMP-1 或 TIMP-2 没有改变。然而，MMP-9 活性的抑制并不影响细胞增殖。有趣的是，只有 MMP-2 的表达，与视网膜母细胞瘤组织中分化的细胞共定位，在视网膜母细胞瘤细胞的分化中显著增加。MMP-2 活性的抑制不影响细胞活力，但减弱了分化的视网膜母细胞瘤细胞的神经突生长和神经丝表达，这是通过抑制 ERK1/2 的激活介导的。
结论
作者认为 MMP-9 和 MMP-2 的差异表达可能反映了视网膜母细胞瘤细胞的生物学特征，如增殖和分化。特别是，MMP-2 可能直接参与视网膜母细胞瘤细胞的分化调节。因此，针对 MMP-2 的治疗性靶向可能通过视网膜母细胞瘤细胞的分化来减少肿瘤的恶性程度。
Zotero 插件