Journal Article

MMP-2 and MMP-9 Expression in Breast Cancer-Derived Human Fibroblasts is Differentially Regulated by Stromal-Epithelial Interactions

Kronsteiner, Nicole, Kubista, Ernst, Kubista, Marion, Marton, Erika, Cullen, Kevin J., Hirtenlehner, Kora, Seifert, Michael, Singer, Christian F.

2002

Overview

Tissue remodeling is a key element in the local invasion and metastasis of malignant breast tumors. The degradation of extracellular matrix that is associated with this process is thought to be mediated by a number of Zn2+-dependent matrix metalloproteinases (MMPs). In most cases these enzymes are not produced by the malignant epithelium itself but by adjacent breast stroma, suggesting an important role for cell-cell interactions. We have analyzed Gelatinase A (MMP-2) and Gelatinase B (MMP-9) gene expression in a panel of six breast cancer cell lines and six primary cultures of stromal cells deriving from breast cancer biopsies. With one exception we did not detect MMP-2 or MMP-9 gene expression in any of the established tumor cell lines. Conversely, tumor stroma-derived fibroblasts expressed MMP-2 mRNA. although no MMP-9 mRNA was seen in RNase protection assays. When fibroblasts were cultured in the presence of media conditioned by MCF-7 tumor cells, MMP-2 enzyme production increased but MMP-9 activity remained undetectable. However, when fibroblasts and MCF-7 tumor cells were co-cultured together, MMP-9 was induced. These observations were confirmed by immunocytochemical analysis of co-cultures of MCF-7 and tumor-derived fibroblasts in which MMP-2 and MMP-9 protein expression was confined to stromal cells adjacent to MCF-7 tumor cells. No MMP-2 or MMP-9 staining was detected in monocultures of the two respective cell types. We conclude that MMP-2 expression is present in the stroma of malignant tumors and is increased by paracrine stimulation mediated by soluble factors. In contrast, MMP-9 expression tumor-derived fibroblasts requires direct contact with malignant tumor epithelium.

• Publisher: Springer,Springer Nature B.V
• Subject: Biological and medical sciences / Breast cancer / Breast Neoplasms - enzymology / Breast Neoplasms - pathology / Cancer research / Cancer therapies / Cell Communication / Epithelial Cells - physiology / Female / Fibroblasts - enzymology / Gene Expression Regulation, Neoplastic / Gynecology. Andrology. Obstetrics / Humans / Mammary gland diseases / Matrix Metalloproteinase 2 - genetics / Matrix Metalloproteinase 2 - metabolism / Matrix Metalloproteinase 9 - genetics / Matrix Metalloproteinase 9 - metabolism / Medical sciences / Stromal Cells - physiology / Tumor Cells, Cultured - metabolism / Tumors