Search

Background: The activity of matrix metalloproteinases (MMPs) in degrading extracellular matrix is controlled by activation of proenzymes and inhibition of MMP tissue inhibitors (TIMPs)., Patients and Methods: To assess the proteolytic cascade imbalance in malignancy progression, tissue expression and serum levels of MMP-2, MMP-9 and of their inhibitors TIMP-2 and TIMP-1 respectively were evaluated in 42 selected patients with high-grade osteosarcoma (OS). MMP-2, MMP-9, TIMP-2 and TIMP-1 were studied in biopsies by immunohistochemistry and in serum by ELISA test. Patients were subdivided into 3 groups according to their follow up: continuously disease-free, diagnosis of metastasis during follow-up, and metastasis at diagnosis., Results: Immunohistochemistry demonstrated an imbalance between MMPs and TIMPs, with a more evident role for MMP-9 than for MMP-2 in tumor progression. TIMP-1 inhibitor in plasma was higher in patients with osteosarcoma than in a control group. This high value of TIMP-1 was particularly evident in the group of patients who later developed metastases and/or local recurrences, and in those with metastases at diagnosis., Interpretation: Our findings confirm the protective action of TIMP-1, as MMP inhibitor, but also show its activity as a growth factor underlining its multifunctional role in OS., (Copyright 2004 Taylor & Francis)

Background: The S100A4 gene may affect the invasive properties of tumor cells through modulation of metalloproteinases (MMPs) and their inhibitors (TIMPs)., Materials and Methods: In the human liposarcoma cell line, SW872, we analyzed the expression of S100A4 protein by immunohistochemistry and flow cytometry. The production of MMP2, MMP9, TIMP1 and TIMP2 was assessed by gelatin zymography and enzyme-linked immunoabsorbent assay before and after interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) stimulation; cell invasiveness was measured by Matrigel invasion assay., Results: S100A4-positive SW872 cells responded to IL-1alpha with induction of immunoreactive MMP2 and TIMP1 and with activation of both MMPs, the latter significantly associated with an increase of cell invasiveness. Treatment with IL-6 induced less significant variations resulting in a more stable invasive behavior., Conclusion: These data show that S100A4-positive SW872 respond to interleukins by influencing the behavior of factors involved in extracellular matrix degradation and emphasize the predominant role of MMP activity status on the positive regulation of cell migration mechanisms.