Department of Medicine, Division of Allergy, Immunology and Rheumatology, State University of New York at Buffalo and Buffalo General Hospital, Kaleida Health, New York 14203, USA.
Immunol Invest. 2011;40(5):447-64. doi: 10.3109/08820139.2011.557795. Epub 2011 Mar 10.
Matrix metallaprotinase-9 (MMP-9) is zinc-containing proteinase whose expression and trafficking are frequently altered in cancer. MMP-9 in the plasma membrane and the secreted forms are thought to contribute to the invasive and metastatic properties of malignant tumors. We have manipulated the expression of MMP-9 in prostate tumor cell line LNCaP and measured their capacity to invade through a basement membrane matrix. Stable expression of human MMP-9 in a poorly metastatic LNCaP prostate cancer cell line produced a 2-3-fold increase in MMP-9 activity and a comparable increase in invasiveness. Transient transfection of LNCaP stable clone expressing MMP-9 with MMP-9 antisense oligonucleotide (ASODN) produced 55-90% less MMP-9 than control cells and were proportionately less invasive. In contrast, manipulating MMP-9 levels had no effect on cell migration across an uncoated membrane. A standard MMP-9 inhibitor at a concentration ranging from 1-10 nM, caused a nearly quantitative inhibition of extracellular MMP-9 activity and had significant effect on basement membrane invasion. Collectively, these results confirm the role of MMP-9 in tissue remodeling associated with prostate tumor invasion.
基质金属蛋白酶-9（MMP-9）是一种含锌的蛋白水解酶，其表达和运输在癌症中经常发生改变。质膜中的 MMP-9 和分泌形式被认为有助于恶性肿瘤的侵袭和转移特性。我们已经操纵了前列腺肿瘤细胞系 LNCaP 中 MMP-9 的表达，并测量了它们穿透基底膜基质的侵袭能力。在低转移性 LNCaP 前列腺癌细胞系中稳定表达人 MMP-9 会使 MMP-9 活性增加 2-3 倍，并使侵袭性增加相当程度。用 MMP-9 反义寡核苷酸（ASODN）瞬时转染表达 MMP-9 的 LNCaP 稳定克隆，产生的 MMP-9 比对照细胞少 55-90%，侵袭性也相应降低。相比之下，操纵 MMP-9 水平对未涂覆膜上的细胞迁移没有影响。浓度范围为 1-10 nM 的标准 MMP-9 抑制剂几乎可以完全抑制细胞外 MMP-9 活性，并对基底膜侵袭有显著影响。总之，这些结果证实了 MMP-9 在与前列腺肿瘤侵袭相关的组织重塑中的作用。
