Furukawa A, Tsuji M, Nishitani M, Kanda K, Inoue Y, Kanayama H, Kagawa S
Department of Urology, School of Medicine, The University of Tokushima, Japan.
Urology. 1998 May;51(5):849-53. doi: 10.1016/s0090-4295(98)00010-7.
To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID).
The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative polymerase chain reaction analysis.
Significantly higher gene expression of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the lines.
MMP-2 and MT1-MMP may have an important role in the invasion mechanism of urothelial cancers.
为阐明基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)在人尿路上皮癌中的作用,我们研究了在严重联合免疫缺陷(SCID)小鼠体内移植的非侵袭性或侵袭性肿瘤细胞系中MMPs、TIMPs和膜型1基质金属蛋白酶(MT1-MMP)的基因表达。
源自膀胱癌的UCT-1肿瘤细胞系是一种无转移证据的非侵袭性可移植肿瘤。源自肾盂肿瘤的UCT-2肿瘤细胞系广泛侵袭但无转移。我们通过半定量聚合酶链反应分析检测了UCT-1和UCT-2中MMPs-1、2、3、7、8、9、10和11、TIMPs-1、2和3以及MT1-MMP的基因表达。
在侵袭性UCT-2肿瘤细胞系中检测到的MMP-2基因表达明显高于非侵袭性UCT-1肿瘤细胞系。虽然两个肿瘤细胞系均表达TIMP-1和MT1-MMP,但在UCT-2肿瘤细胞系中观察到的MT1-MMP基因表达强于UCT-1肿瘤细胞系。在两个细胞系中均未检测到其他MMPs或TIMPs。
MMP-2和MT1-MMP可能在尿路上皮癌的侵袭机制中起重要作用。