By Wen G Jiang; R E Mansel
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From its advent, oncological chemotherapy has been laden through its bad selectivity simply because such a lot antiproliferative medicines are poisonous not just to tumor cells but in addition to special populations of the body’s non-neoplastic cells. the consequent issues of unwanted effects are compounded by way of problems in predicting the specified efficiency of chemotherapy in person sufferers.
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Manipulation of MMP-9 can also be seen to affect metastasis. In a sarcoma model system in which MMP-9 expression correlated with the ability to metastasize, over-expression of MMP-9 those cell lines lacking MMP-9 expression induced metastatic potential. Tumor growth was unaffected (Bernhard et al, 1994). Similar experiments in melanoma cells also demonstrated the ability of MMP-9 to augment metastasis (MacDougall et al, 1999). In complementary experiments, downregulation of MMP-9 using a ribozyme, curtailed metastasis in a sarcoma model system or a prostatic carcinoma model, while this down regulation did not alter tumor growth rate (Hua and Muschel, 1996; Sehgal et al, 1998).
Eitzman DT, Krauss JC, Shen T, Cui J, Ginsburg. Lack of plasminogen activator inhibitor-1 effect in a transgenic mouse model of metastatic melanoma. Blood 1996; 87: 4718–4722. Fazioli F, Resnati M, Sidenius N, Higashimoto Y, Appella E, Blasi F. A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity. EMBO J 1997; 16: 7279–7286. Fischer K, Lutz V, Wilhelm O, et al. Urokinase induces proliferation of human ovarian cancer cells: characterization of structural elements required for growth factor function.
Stromelysin deficient mice still can activate MMP-9 in a model system based upon endothelial injury (Lijnen et al, 1999). The activation of MMP-2 has been correlated with tumor progression and is required for invasion suggesting that expression MT1-MMP expression may be a controlling event (Nagase, 1998). The activation and significance of the activation of MMP-9 is less carefully documented. 4. SUBSTRATES Initially the MMPs were defined by their ability to degrade extracellular matrix and both MMP-2 and 9 fit that pattern with activity against denatured collagens of many types including collagens Type IV and V, elastin, gelatin, and fibronectin.