Ohtani H, Motohashi H, Sato H, Seiki M, Nagura H
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Int J Cancer. 1996 Nov 27;68(5):565-70. doi: 10.1002/(SICI)1097-0215(19961127)68:5<565::AID-IJC2>3.0.CO;2-X.
Membrane-type metalloproteinase-I (MTI-MMP) is a transmembrane metalloproteinase, which activates pro-gelatinase A. There has been disagreement as to whether the cell types expressing MTI-MMP are cancer cells or stromal fibroblasts. Using human gastrointestinal carcinomas, the present study disclosed the tissue localization of MTI-MMP mRNA by in situ hybridization and ultrastructural localization of its protein by immunoelectron microscopy. In normal colon and stomach tissues, MTI-MMP mRNA and protein were negative or faintly positive both in epithelial cells and in stromal fibroblasts, except in the fundic gland of the stomach, which showed the positivity for MTI-MMP. In contrast, gastrointestinal cancer tissue showed over-expression of MTI-MMP mRNA and protein both in cancer cells and in stromal cells (fibroblasts). Stromal fibroblasts also expressed mRNA for gelatinase A and type-I procollagen. Double immunohistochemistry revealed that macrophages were also positive for MTI-MMP. Immunoelectron microscopy showed that MTI-MMP was localized along the plasma membrane of cancer cells and macrophages and in rough endoplasmic reticulum of fibroblasts. The present study reveals a dual over-expression pattern of MTI-MMP both in cancer cells and in stromal fibroblasts; the expression in cancer cells may be related to the invasive growth, whereas that in fibroblasts may be related to the tissue remodeling process caused by invasive growth of cancer cells.
膜型金属蛋白酶-I（MTI-MMP）是一种跨膜金属蛋白酶，可激活前明胶酶A。关于表达MTI-MMP的细胞类型是癌细胞还是基质成纤维细胞，一直存在分歧。本研究利用人类胃肠道癌，通过原位杂交揭示了MTI-MMP mRNA的组织定位，并通过免疫电子显微镜对其蛋白质进行了超微结构定位。在正常结肠和胃组织中，除胃底腺显示MTI-MMP阳性外，上皮细胞和基质成纤维细胞中的MTI-MMP mRNA和蛋白质均为阴性或弱阳性。相比之下，胃肠道癌组织在癌细胞和基质细胞（成纤维细胞）中均显示MTI-MMP mRNA和蛋白质的过度表达。基质成纤维细胞也表达明胶酶A和I型前胶原的mRNA。双重免疫组织化学显示巨噬细胞对MTI-MMP也呈阳性。免疫电子显微镜显示，MTI-MMP定位于癌细胞和巨噬细胞的质膜以及成纤维细胞的粗面内质网。本研究揭示了MTI-MMP在癌细胞和基质成纤维细胞中的双重过度表达模式；癌细胞中的表达可能与侵袭性生长有关，而成纤维细胞中的表达可能与癌细胞侵袭性生长引起的组织重塑过程有关。
