Abstract
Own results of long-term studies of expression of matrix metalloproteinases (MMPs) and their endogenous regulators examined in fibroblasts transformed by oncogene E7 HPV16 (TF), immortalized fibroblasts (IF), cell lines associated with HPV16 and HPV18, and tumor tissue samples from patients with squamous cervical carcinoma (SCC) associated with HPV16 have been summarized. 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. MMP expression correlated with the tumorigenic of transformed clones. Expression of MMP-9 was found only in TF. In TF expression mRNA TIMP-1 decreased, while expression of the genatinase inhibitor, TIMP-2, increased. Collagenase activity and expression of the MMP-14 (collagenase) mRNA increased, while gelatinase activity remained unchanged. The destructive potential of TF is associated with induction of collagenases, gelatinase MMP-9 and decreased levels of MMP inhibitors. MMP-9 may serve as a TF marker. 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). 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-2 activity significantly increased in Caski and HeLa cell lines, while MMP-9 expression in these cell lines was not detected. The comparative study of expression MMP of 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 associated with increased expression of collagenases MMP-1, MMP-14 and gelatinase MMP-9, as well as decreased expression of inhibitors (TIMP-1 and TIMP-2), and to a lesser extent with increased expression of MMP-2. MMP-1 and MMP-9 can serve as markers of invasive and metastatic potential of the SCC tumor. The morphologically normal tissue adjacent to the tumor tissue is characterized by significant expression of MMP-1, MMP-2, and MMP-9. This also contributes to the increased destructive potential of the tumor.
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Hadler-Olsen, E., Winberg, J.O., and Uhlin-Hansen, L., Tumor Biol., 2013, vol. 34, pp. 2041–2051. doi 10.1007/s13277-013-0842-8
Fingelton, B., Front Biosc., 2006, vol. 11, pp. 479–491.
Solovyeva, N.I., Vopr. Med. Khim., 2000, vol. 46, pp. 489–490.
Willis, A.L., Sabeh, F., Li, X.Y., and Weiss, S.J.J., Microsc. Sep., 2013, vol. 251, pp. 250–260. doi 10.1111/jmi.12064
Murphy, G. and Nagase, H., Mol. Aspects Med., 2008, vol. 29, pp. 2900–3086. doi 10.1016/j.mam.2008.05.002
Visse, R. and Nagase, H., Circ. Res., 2003, vol. 92, pp. 827–839.
Mannello, F. and Medda, V., Progr. Histochem. Cytochem., 2012, vol. 47, pp. 27–58. doi 10.1016/j.proghi.2011.12.002
Kessenbrock, K., Plaks, V., and Werb, Z., Cell, 2010, vol. 141, pp. 52–67. doi 10.1016/j.cell.2010.03.015
Rodríguez, D., Morrison, C.J., and Overall C.M., Biochim. Biophys. Acta, 2010, vol. 1803, pp. 39–54. doi 10.1016/j.bbamcr.2009.09.015
Cathcart, J., Pulkoski-Gross, A., and Cao, J., Genes Dis., 2015, vol. 2, pp. 26–34.
Kugaevskaya, E.V., Timoshenko, O.S., and Solovyeva, N.I., Biomed. Khim., 2015, vol. 61, pp. 683–688. doi 10.18097/PBMC20156103301
Shuman Moss, L.A., Jensen-Taubman, S., and Stetler-Stevenson, W.G., Am. J. Pathol., 2012, vol. 181, pp. 1895–1899. doi 10.1016/j.ajpath.2012.08.044
Gialeli, C., Theocharis, A.D., and Karamanos, N.K., FEBS J., 2011, vol. 278, pp. 16–27. doi 10.1111/j.1742-4658.2010.07919.x
Kessenbrock, K., Wang, C.Y., and Werb, Z., Matrix Biol., 2015, vols. 44–46, pp. 184–190. doi 10.1016/j.matbio.2015.01.022
Jacob, A. and Prekeris, R., Front. Cell. Dev. Biol., 2015, vol. 3, p. 4. doi 10.3389/fcell.2015.00004
Bauvois, B., Biochim. Biophys. Acta, 2012, vol. 1825, pp. 29–36. doi 10.1016/j.bbcan.2011.10.001.
Solovyeva, N.I., Bioorgan. Khim., 1998, vol. 24, pp. 217–226.
Jiang, W.G., Sanders, A.J., and Katoh, M., Semin. Cancer Biol., 2015, pii: S1044–579X(15)00023-1. doi 10.1016/j.semcancer.2015.03.008
Makarkina, O.M. and Rodionova, A.A., Vademecum, 2014, vol. 17, pp. 22–29.
zur Hausen, H., Biochim Biophys Acta, 1996, vol. 1288, pp. 55–78.
zur Hausen, H., Virology, 2009, vol. 384, pp. 260–265. doi 10.1016/j.virol.2008.11.046.
Wang, H., Zhang, X., Huang, L., Li, J., Qu, S., and Pan, F., Cell Biochem. Biophys., 2014, vol. 70, pp. 729–734. doi 10.1007/s12013-014-9974-8
Zhu, D., Ye, M., and Zhang, W., Int. J. Clin. Exp. Pathol., 2015, vol. 8, pp. 4981–4989.
McLaughlin-Drubin, M.E. and Münger, K., Virology, 2009, vol. 384, pp. 335–344. doi 10.1016/j.virol.2008.10.006
Moody, C.A. and Laimins, L.A., Nat. Rev. Cancer, 2010, vol. 10, pp. 550–560. doi 10.1038/nrc2886.
Kisseljov, F.L., Imyanitov, E.N., Kisseljova, N.P., and Levina, E.S., in Molekulyarnaya onkologiya: ot virusnoi teorii k lecheniyu raka (Molecular Oncology: From Virus Theory to Cancer Treatment), Orlova, G.M., Ed., Moscow: GEOS, 2013, pp. 40–46.
Fullár, A., Dudás, J., Oláh, L., Hollósi, P., Papp, Z., and Sobel, G., BMC Cancer, 2015, vol. 15, p. 256. doi 10.1186/s12885-015-1272-3
Matheus, E.R., Zonta, M.A., Discacciati, M.G., Paruci, P., Velame, F., and Cardeal, L.B., Diagn. Cytopathol., 2014, vol. 42, pp. 827–833. doi 10.1002/dc.23124
Li, Y., Wu, T., Zhang, B., Yao, Y., and Yin, G., Med. Oncol., 2012, vol. 29, pp. 3394–3399. doi 10.1007/s12032-012-0283z
Cardeal, L.B., Boccardo, E., Termini, L., Rabachini, T., Andreoli, M.A., di Loreto, C., Longatto Filho, A., Villa, L.L., and Maria-Engler, S.S., PLoS One, 2012, vol. 7. e33585. doi 10.1371/journal.pone.0033585
Komissarova, E.V., Soyfer, M.V., Pavlova, L.S., and Kisseljov, F.L., Oncol. Rep., 1995, vol. 2, pp. 1169–1174.
Zhurbitskaya, V.A., Savel’eva, L.V., Zelenin, A.V., and Kisseljov, F.L., Mol. Biol. (Moscow), 1999, vol. 33, pp. 243–247.
Yartseva, N., Komissarova, E., Zhurbitskaya, V., Kisseljova, N., Pavlova, L., Fedortseva, R., and Kisseljov, F., Oncol. Rep., 1997, vol. 4, pp. 629–635.
Solovyeva, N.I., Vinokurova, S.V., Dilakyan, E.F., Gureeva, T.A., Zhurbitskaya, V.A., and Balaevskaya, T.O., Vopr. Med. Khim., 2001, vol. 47, pp. 72–79.
Ryzhakova, O.S., Gureeva, T.A., Zhurbitskaya, V.A., and Solovyeva, N.I., Biomed. Khim., 2007, vol. 53, pp. 322–331.
Solovyeva, N.I., Vinokurova, S.V., Ryzhakova, O.S., Gureeva, T.A., and Tsvetkova, I.V., Biomed. Khim., 2009, vol. 55, pp. 441–450.
Ryzhakova, O.S. and Solovyeva, N.I., Biomed. Khim., 2013, vol. 59, pp. 530–540. doi 10.18097/pbmc20135905530
Solovyeva, N.I., Ryzhakova, O.S., Kisseleva, N.P., Zavalishina, L.E., Andreeva, Ju.Ju., and Frank, G.A., Cancer Res. J., 2010, vol. 4, pp. 59–72.
Solovyeva, N.I., Timoshenko, O.S., Kugaevskaya, E.V., Andreeva, Ju.Ju., and Zavalishina, L.E., Bioorgan. Khim., 2014, vol. 40, pp. 743–751.
Solovyeva, N.I., Ryzhakova, O.S., Kisseleva, N.P., Zavalishina, L.E., Andreeva, J.J., and Frank, G.A., in Advancements in Cancer Research, Viktorsson, K., Ed., New York: Nova Science Publishers, 2012, pp. 61–74.
Ryzhakova, O.S., Zavalishina, L.E., Andreeva, J.J., and Solovyeva, N.I., Biomed. Khim., 2013, vol. 59, pp. 55–64. doi 10.18097/pbmc20135901055
Timoshenko, O.S., Kugaevskaya, E.V., Gureeva, T.A., Zavalishina, L.E., Andreeva, J.J., Frank, G.A., and Solovyeva, N.I., Arkhiv Patologii, 2015, vol. 77, pp. 31–35.
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Original Russian Text © N.I. Solovyeva, O.S. Timoshenko, T.A. Gureeva, E.V. Kugaevskaya, 2016, published in Biomeditsinskaya Khimiya.
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Solovyeva, N.I., Timoshenko, O.S., Gureeva, T.A. et al. Matrix metalloproteinases and their endogenous regulators in squamous cervical carcinoma (A review of own results). Biochem. Moscow Suppl. Ser. B 10, 110–121 (2016). https://doi.org/10.1134/S1990750816020116
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DOI: https://doi.org/10.1134/S1990750816020116