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Metaloproteinazy – znaczenie w procesie nowotworzenia, diagnostyce i terapii

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Pietrzak J., Mirowski M.

Folia Medica Lodziensia

2015

vol. 42

issue 1

33-48

Metalloproteinases (MMP) are proteolytic enzymes whose activity is determined by the presence of zinc ion in the active site and are a widely distributed family of protease to ensure the preservation of homeostasis in animals. In human body they also play many important functions participating in the process of embryogenesis as well as in the formation of blood cells or bone formation. The main role, as it seemed at the beginning research on this group of enzymes, was to digest the extracellular matrix. However, over the years, it turned out that metalloproteinases are important part in the regulation of cell biology, in particular a tumor cell. Studies have confirmed the participation of metalloproteinases in all stages of the process of carcinogenesis. At the moment, there are numerous reports of available of various MMPs in different tumors. However, two of these MMP–2 and MMP–9 belonging to the gelatinases seem to be the most common. It has been confirmed also that higher levels usually indicate a worse prognosis for the patient. Therefore, they may prove to be a valuable prognostic indication for clinicians. Attention was paid to the potential use of matrix metalloproteinases in targeted therapy. The pharmaceutical industry has long been trying to launch metalloproteinase inhibitors as possible therapeutics in cancer, seeing in them a potential that, however, is limited to the early stages of development. After initial setbacks related primarily to the low selectivity is used at once more modern methods as monoclonal antibodies or liposomal drug delivery system. Thus, giving the possibility of treatment that does not cause so enormous side effects as conventional therapy.

Charakterystyka elektroforetyczna aktywności metaloproteinazowej surowicy pacjentów z przewlekłą białaczką limfocytową – badania wstępne

80%

Pietrzak J., Wodziński D., Franiak-Pietryga I., Mirowski M.

Folia Medica Lodziensia

2015

vol. 42

issue 1

49-62

Metalloproteinases play an important role in the development and metastasis of many cancers. Their activity is also an important component of tumorgenesis associated processes such as angiogenesis, decreased apoptosis, or unlimited proliferation of pathological cells. In this study we tried to estimate a differences of metalloproteinase activity digesting the gelatin in the sera of patients with chronic lymphocytic leukemia and healthy people, by the zymographic technique. To confirm that the gelatinolytic activity originated from the metalloproteinases their specific inhibitors: phenanthroline and ethylene– diaminetetraacetic acid were used. In patient’s sera a zymographic analysis revealed the presence of additional activity. The first of them are located in a region corresponding to a molecular weight of approximately 240 kDa, probably corresponds to the dimer of proMMP–9. Another two active fractions present in the sera of patients suffering from leukemia corresponded to a molecular weight of about 110 and 130 kDa probably represents a complex of proMMP–9 with lipocain. In a control sera, only one activity could be observed exhibiting a molecular weight of about 110 kDa, which is stronger than corresponding fraction in patient’s sera. The biggest difference between the two investigated sera was gelatynolytic activity located in the region of a molecular weight of about 94 kDa, which probably corresponded to proMMP–9. In some leukemic sera this activity was several times higher compared to the control samples, in which there was a constant and relatively low level of it. Despite significant activity of proMMP–9 in sera of patients with CLL no biologically active equivalent band of molecular weight 84 kDa were detected. The fractions which corresponded to different forms of MMP–2 (72, 64 kDa) were present in the sera of tumor and control, although proMMP–2 was more strongly expressed in the control samples.

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2 Folia Medica Lodziensia

2 2015

2 Mirowski M.

2 Pietrzak J.

1 Franiak-Pietryga I.

1 Wodziński D.

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Metaloproteinazy – znaczenie w procesie nowotworzenia, diagnostyce i terapii

Charakterystyka elektroforetyczna aktywności metaloproteinazowej surowicy pacjentów z przewlekłą białaczką limfocytową – badania wstępne