Differential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor and stromal cells of squamous cell carcinomas of the lung

Abstract

Matrix metalloproteinases (MMPs) play a key role in cancer progression. Interstitial collagenase (MMP-1) and type IV collagenases (MMP-2, MMP-9) are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. Besides tumor cells, fibroblasts are especially involved in MMP production. The aim of this study was to quantify MMP-1, MMP-2 and MMP-9 within tumor cells and tumor-surrounding fibroblasts compared to normal lung epithelial cells to gain an insight into the function of these MMPs in squamous cell carcinomas of the lung. The expression and activity of MMP-1, MMP-2 and MMP-9 were analyzed in 30 squamous cell carcinomas and in normal lung tissue from the same patients by immunohistology and gelatin zymography. The majority of tumor cells were positive for MMP-1 (mean +/- SD: 67.3 +/- 26.7%) and MMP-9 (64.7 +/- 22.8%), whereas a significantly lower percentage of normal bronchoepithelial cells (47.3 +/- 25.4 and 40.3 +/- 24.2%, respectively; p < 0.01) and fibroblasts located in the tumor-surrounding tissue (39.7 +/- 14.3 and 38.1 +/- 24.1%, respectively; p < 0.01) expressed these MMPs. Only a few tumor cells showed any immunoreactivity for MMP-2 (4.4 +/- 6.7%), whereas a higher percentage of fibroblasts tested positive for this enzyme (8.6 +/- 13.1%; p < 0.01). Using gelatin zymography, we could demonstrate that MMP-2 is activated in the tumor only, not in normal lung tissue. The coordinated expression of MMP-1, MMP-2 and MMP-9 in tumor cells and/or their induction in tumor-surrounding fibroblasts and further activation in the tumor tissue may be involved in the high invasive and metastatic potential of squamous cell carcinomas of the lung. Comparing the results from immunohistology and zymography can give indications for distribution and activity of proteinases, especially certain MMPs such as MMP-2.