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Title: [Matrix metalloproteinases and their endogenous regulators in squamous cervical carcinoma (review of the own data)]. Author: Solovуeva NI, Timoshenko OS, Gureeva TA, Kugaevskaya EV. Journal: Biomed Khim; 2015; 61(6):694-704. PubMed ID: 26716740. Abstract: Expression of matrix metalloproteinases (MMPs) and their endogenous regulators has been investigated in squamous cervical carcinoma (SCC). The study included (i) immortalized fibroblasts (IF) and three clones of fibroblasts transformed by oncogene E7 HPV-16 (TF); (ii) cell lines associated with HPV-16 and HPV-18; (iii) tumor tissue samples from patients with SCC, associated with gene E7 HPV-16. Transfection of fibroblasts with the E7 HPV16 oncogen was accompanied by induction of collagenase (MMP-1, MMP-14) and gelatinase (MMP-9) gene expression and the increase in catalytic activity of these MMP, while gelatinase MMP-2 expression remained unchanged. Expression of MMP-9 was found only inTF. MMP-9 may serve as a TF marker. In TF expression mRNA TIMP-1 was decreased. The level of free endogenous inhibitors in TF was significantly lower then the level in IF. Expression MMP correlated with the tumorigenic potential of TF. Invasive potential of cell lines associated with HPV18 (HeLa and S4-1) was more pronounced than that of cell lines associated with HPV16 (SiHa and Caski). The cell lines differed substantially in the level of expression of MMPI and their endogenous regulators. In most cell lines mRNA levels of collagenases MMP-1 and MMP-14 and the activator (uPA) increased, while gelatinase MMP-2 mRNA and tissue inhibitors mRNAs changed insignificantly. MMP-9 expression in cell lines was not detected. Results of studies on these cell lines suggest existence of an imbalance in the system enzyme/inhibitor/activator, that increases destructive potential of these cells. The study of expression of MMP and their endogenous regulators performed using SCC tumor samples associated with HPV16 has shown that the invasive and metastatic potentials of tumor tissue in SCC is obviously determined by the increase of expression of collagenases MMP-1, MT1-MMP and gelatinase MMP-9, decreased expression of inhibitors (TIMP-1 and TIMP-2), and to a lesser extent to increased expression of MMP-2. MMP-1 and MMP-9 can serve as markers of invasive and metastatic potential of the SCC tumor. In adjacent to the tumor normal tissue revealed a significant expression of MMP-1,-2,-9. Obobshcheny rezul'taty sobstvennykh mnogoletnikh issledovaniĭ osobennosteĭ ékspressii matriksnykh metalloproteinaz (MMP) i ikh éndogennykh reguliatorov v transformirovannykh onkogenom E7 HPV-16 fibroblastakh (TF), immortalizovannykh fibroblastakh (IF), na liniiakh kletok, assotsiirovannykh s HPV-16 i HPV-18; na klinicheskikh obraztsakh opukholevykh tkaneĭ ploskokletochnoĭ kartsinomy sheĭki matki (PKShM), assotsiirovannykh s HPV-16 Transfektsiia fibroblastov onkogenom E7 HPV16. soprovozhdalas' induktsieĭ ékspressii genov kollagenaz – MMP-1, MMP-14 i zhelatinazy MMP-9 i uvelicheniem ikh aktivnosti; ékspressiia zhelatinazy MMP-2 sushchestvenno ne izmenialas'. Ékspressiia MMP korrelirovala s tumorogennym potentsialom transformirovannykh klonov; ékspressiia MMP-9 obnaruzhena tol'ko v TF; ékspressiia mRNK ingibitora kollagenaz TIMP-1 v TF snizhalas', a ékspressiia ingibitora zhelatinaz – TIMP-2 uvelichivalas'. V IF neznachitel'no uvelichivalas' aktivnost' kollagenaz i ékspressiia mRNK kollagenazy MMP-14, aktivnost' zhelatinaz ne izmenialas'. Destruktivnyĭ potentsial TF obuslovlen induktsieĭ ékspressii kollagenaz, zhelatinazy MMP-9 i snizheniem urovnia ingibitorov MMP. MMP-9 mozhet sluzhit' markerom TF. Invazivnyĭ potentsial v liniiakh HeLa i S4-1, assotsiirovannykh s HPV18, bolee vyrazhen, chem v liniiakh SiHa i Caski, assotsiirovannykh s HPV16. Ékspressiia mRNK kollagenaz MMP-1, MMP-14, i aktivatora – uAP v bol'shinstve issledovannykh liniĭ kletok uvelichivalas'; ékspressiia mRNK zhelatinazy MMP-2 i ingibitorov sushchestvenno ne izmenialas'. Aktivnost' MMP-2 v liniiakh Caski i HeLa uvelichivalas', ékspressiia MMP-9 v liniiakh kletok ne obnaruzhena. Uvelichenie destruktivnogo potentsiala v kletochnykh liniiakh obuslovleno uvelicheniem ékspressii kollagenaz i nizkim urovnem ékspressii ingibitorov MMP. Sravnitel'noe issledovanie ékspressii MMP, provedennoe na assotsiirovannykh s E7 HPV16 obraztsakh opukholeĭ PKShM v prisutstvii ili otsutstvie metastazov, pokazalo, chto osnovnoĭ vklad v invazivnyĭ i metastaticheskiĭ potentsialy opukholeĭ vnosit uvelichenie ékspressii kollagenaz MMP-1, MMP-14, zhelatinazy MMP-9 i snizhenie ékspressii ingibitorov TIMP-1, TIMP-2, i v men'sheĭ stepeni – uvelichenie ékspressii MMP-2. MMP-1 i MMP-9 mogut sluzhit' markerami invazivnogo i metastaticheskogo potentsiala opukholeĭ pri PKShM. V prilegaiushcheĭ k opukholi morfologicheski normal'noĭ tkani obnaruzhena sushchestvennaia ékspressiia MMP-1, MMP-2, MMP-9, chto vnosit svoĭ dopolnitel'nyĭ vklad v uvelichenie destruktivnogo potentsiala opukholi.[Abstract] [Full Text] [Related] [New Search]