Dual over-expression pattern of membrane-type metalloproteinase-1 in cancer and stromal cells in human gastrointestinal carcinoma revealed by in situ hybridization and immunoelectron microscopy

Abstract

Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase, which activates pro-gelatinase A. There has been disagreement as to whether the cell types expressing MT1-MMP are cancer cells or stromal fibroblasts. Using human gastrointestinal carcinomas, the present study disclosed the tissue localization of MT1-MMP mRNA by in situ hybridization and ultrastructural localization of its protein by immunoelectron microscopy. In normal colon and stomach tissues, MT1-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 MT1-MMP. In contrast, gastrointestinal cancer tissue showed over-expression of MT1-MMP mRNA and protein both in cancer cells and in stromal cells (fibroblasts). Stromal fibroblasts also expressed mRNA for gelatinase A and type-1 procollagen. Double immunohistochemistry revealed that macrophages were also positive for MT1-MMP. Immunoelectron microscopy showed that MT1-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 MT1-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.