Ohnishi Yoshihiro, Ito Yoshiyasu, Tajima Shingo, Ishibashi Akira, Arai Katsuhiko
Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Saitama, Japan.
J Dermatol Sci. 2002 Feb;28(2):119-25. doi: 10.1016/s0923-1811(01)00159-1.
Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. Enhanced expression of matrix metalloproteinase-2 (MMP-2) has been demonstrated in dermatofibroma (DF) and malignant fibrous histiocytoma (MFH). MMP-2 has been shown to be activated by membrane-type MMPs (MT-MMPs). To study the role of MT-MMP in the activation of MMP-2, skin specimens of DF (five cases) and MFH (three cases) were immunohistochemically studied using in situ zymography and the antibodies against matrix metalloproteinase-2 (MMP-2) and membrane type 1-3-MMPs (MT1-3-MMPs). Both MMP-2 activity and its expression were significantly activated in the tumor cells in DF and MFH. Anti-MT2-MMP strongly reacted with tumor cells of all cases of DF and MFH, whereas anti-MT1 or 3-MMP antibody showed a weak reaction in some cases of DF and MFH. Double immunofluorescence labeling demonstrated that the immunoreactive cells with anti-MMP-2 antibody in DF and MFH consistently reacted with anti-MT2-MMP antibody. The results suggest that the activation of MMP-2 in the benign and malignant fibrous tumors is related to the activation of MT-MMPs.
基质金属蛋白酶（MMPs）在肿瘤侵袭和转移中起重要作用。已证实在皮肤纤维瘤（DF）和恶性纤维组织细胞瘤（MFH）中基质金属蛋白酶-2（MMP-2）的表达增强。MMP-2已被证明可被膜型基质金属蛋白酶（MT-MMPs）激活。为研究MT-MMP在MMP-2激活中的作用，采用原位酶谱法以及抗基质金属蛋白酶-2（MMP-2）和膜型1-3基质金属蛋白酶（MT1-3-MMPs）的抗体，对5例DF和3例MFH的皮肤标本进行了免疫组织化学研究。DF和MFH的肿瘤细胞中MMP-2活性及其表达均显著激活。抗MT-Ⅱ-MMP与所有DF和MFH病例的肿瘤细胞均发生强烈反应，而抗MT-Ⅰ或3-MMP抗体在部分DF和MFH病例中反应较弱。双重免疫荧光标记显示，DF和MFH中抗MMP-2抗体的免疫反应细胞始终与抗MT-Ⅱ-MMP抗体发生反应。结果表明，良性和恶性纤维性肿瘤中MMP-2的激活与MT-MMPs的激活有关。
