Monitoring mmp-9 gene expression in stromal cells using a novel transgenic mouse model.

Abstract

Matrix metalloproteinase (MMP)-9 (gelatinase B) is involved in extracellular matrix degradation in the context of the motility and in in vivo migration of normal and malignant cells. Accordingly, its expression is highly regulated at the transcriptional level. In several types of human cancers, MMP-9 expression is abnormally elevated and has been associated with poor prognosis. Such high levels of MMP-9 expression are found in tumor cells and in stromal components. Therefore, it is important to understand the spatiotemporal expression pattern of MMP-9 in tissues for the development of effective therapeutic strategies that are aimed at suppressing mmp-9 gene activation. In the present work, we describe a transgenic mouse model harboring a luciferase gene under the control of the murine mmp-9 promoter. We found that the expression pattern of the transgene was similar to that of the endogenous mmp-9 gene either constitutively or following inflammatory stimuli. A constitutive transgene expression was observed in the bone marrow, consistent with the observed high levels of endogenous mmp-9 gene expression normally found in the bone. LPS injection in mice also induced a consistent and significant increase in bioluminescent signals in the liver, which is a major target of LPS-induced septic shock. Finally, we further used the model to provide evidence that mmp-9 is activated in stromal cells of the lung and spleen in melanoma tumor-bearing mice. This bioluminescent imaging model may facilitate in vivo monitoring of MMP-9 activation in stromal cells in tumor progression and inflammatory diseases.