PROCATHEPSIN B AND ENDOGENOUS INHIBITORS OF CYSTEINE PROTEASES IN TUMORS OF REPRODUCTIVE SYSTEM


Cite item

Full Text

Abstract

Cysteine proteases are regulated by the rate of the conversion of their inactive proforms into active forms and by specific endogenous inhibitors (cystatins), playing the important role in their regulation, especially in tumor growth and metastasis process. The content of procatepsin B, endogenous inhibitors of cysteine proteases cystatin B and cystatin C in biological fluids (blood serum, ascites fluid) in women with malignant neoplasms of the genital organs was studied. The comparative study of the concentration of procotepsin B, cystatin B and C in blood serum in practically healthy women and women with tumors of the reproductive system was carried out with the use of the enzyme immunoassay nethod. A high content of procatepsin B was shown to be found in all the study groups. The concentration of cystatin B was within the limits of significance and concentration of cystatin C was not changed in same patients in the study groups as compared with the control. The level of cystatin C in the serum was found to be correlated with the progression of the disease. In ascitic fluid (in comparison with blood serum), a sharp increase in the concentration of procatepsin B was revealed, reflecting its elevated extracellular secretion by tumor cells.

About the authors

Elena A. Gashenko

Scientific Research Institute of Physiology & Basic Medicine

Email: elena.gashenko@gmail.com
MD, Researcher of the Laboratory of Experimental Models of Neuron Degenerative Processes. Novosibirsk, 630117, Russian Federation Novosibirsk, 630117, Russian Federation

V. A Lebedeva

Novosibirsk State Medical University

Novosibirsk, 630091, Russian Federation

G. S Russkikh

Scientific Research Institute of Biochemistry

Novosibirsk, 630117, Russian Federation

E. A Tsykalenko

Novosibirsk State Medical University

Novosibirsk, 630091, Russian Federation

A. B Pupyshev

Scientific Research Institute of Physiology & Basic Medicine

Novosibirsk, 630117, Russian Federation

I. V Brak

Scientific Research Institute of Physiology & Basic Medicine

Novosibirsk, 630117, Russian Federation

T. A Korolenko

Scientific Research Institute of Physiology & Basic Medicine

Novosibirsk, 630117, Russian Federation

References

  1. Каприн А.Д., Старинский В.В., Петрова Г.В., ред. Злокачественные новообразования в России в 2015 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИРЦ» Минздрава России; 2017.
  2. Joyce J.A., Baruch A., Chehade K., Meyer-Morse N., Giraudo E., Tsai F.Y. et al. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell. 2004; 5(5): 443-53.
  3. Elliott E., Sloane B.F. The procathepsin B in cancer. Perspect. Drug Des. 1996; (6): 12-32.
  4. Tan G.J., Peng Z.K., Lu J.P., Tang F.Q. Cathepsins mediate tumor metastasis. World J. Biol. Chem. 2013; 26; 4(4): 91-101.
  5. Turk V., Stoka V., Vasiljeva O., Renko M., Sun T., Turk B., Turk D. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta. 2012; 1824(1): 68-88.
  6. Короленко Т.А. Цистатины - биологическая роль и нарушения в патологии. Вестник Российской АМН. 2008; (4): 43-7.
  7. Turk V., Stoka V., Turk D. Cystatins: biochemical and structural properties, and medical relevance. Front. Biosci. 2008, 13, 5406-20.
  8. Levičar N., Kos J., Blejec A., Golouh R., Vrhovec I., Frkovič-Grazio S., Lah T. Comparison of potential biological markers cathepsin B, cathepsin L, stefin A and stefin B with urokinase and plasminogen activator inhibitor-1 and clinicopathological data of breast carcinoma patients. Cancer Det. Prev. 2002; 26: 42-9.
  9. Спирина Л.В., Кондакова И.В. Роль специфического внутриклеточного протеолиза в онкогенезе. Вопр. онкол. 2008; 54(6): 690-4.
  10. Korolenko T.A., Kisarova Y.A, Filjushina E.E., Machova E. In: Macrophages: Life Cycle, Functions and Diseases (Takahashi R., Kai H. Eds.). New York: Nova Science Publishers; 2012: 249-76.
  11. Гашенко Е.А., Лебедева В.А., Короленко Т.А., Гаврилова Н.И., Филатова Т.Г., Цикаленко Е.А. и др. Концентрация прокатепсина В и ингибитора цистеиновых протеаз в биологических жидкостях при развитии опухолей. Бюллетень СО РАМН. 2010; 30(4):110-5.
  12. Kos J., Krasovec M., Cimerman N., Nielsen H.J., Christensen I.J., Brünner N. Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis. Clin. Cancer Res. 2000; 6(2): 505-11.
  13. Wegiel B., Jiborn T., Abrahamson M., Helczynski L., Otterbein L., Persson J.L., Bjartell A. Cystatin C is downregulated in prostate cancer and modulates invasion of prostate cancer cell via MAPK/Erk and androgen receptor pathways. PLoS One. 2009; 4(11): e7953.
  14. Gashenko E.A., Lebedeva V.A., Brak I.V., Tsykalenko E.A., Vinokurova G.V., Korolenko T.A. Evaluation of serum procathepsin B, cystatin B and cystatin C as possible biomarkers of ovarian cancer». Int. J. Circumpolar Health. 2013, 72: 21215.
  15. Kolwijck E., Kos J., Obermajer N., Span P.N., Thomas C.M., Massuger L.F. et al. The balance between extracellular cathepsins and cystatin C is of importance for ovarian cancer. Eur. J. Clin. Invest. 2010; 40: 591-9.
  16. Lah T.T., Kokalj-Kunovar M., Kastelic L., Babnik J., Stolfa A., Rainer S. et al. Cystatins and stefins in ascites fluid from ovarian carcinoma. Cancer Lett. 1992; 61: 243-53.
  17. Nishikawa H., Ozaki Y., Nakanishi T., Blomgren K., Tada T., Arakawa A. et al. The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer. Gynecol. Oncol. 2004; 92(3): 881-6.
  18. Takaya A., Peng W.-X., Ishino K., Kudo M., Yamamoto T., Wada R. et al. Cystatin B as a potential diagnostic biomarker in ovarian clear cell carcinoma. Int. J. Oncol. 2015; 46(4): 1573-81. doi: 10.3892/ijo.2015.2858
  19. Kolwijck E., Massuger L.F., Thomas C.M., Span P.N., Krasovec M., Kos J. et al. Cathepsins B, L and cystatin C in cyst fluid of ovarian tumors. J. Cancer Res. Clin. Oncol. 2010; 136: 771-8.
  20. Mussap M., Plebani M. Biochemistry and clinical role of human cystatin C. Crit. Rev. Clin. Lab. Sci. 2004; 41(5-6): 467-550.
  21. Kos J., Lah T.T. Cysteine proteases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review). Oncol. Rep. 1998; 5(6): 1349-61.
  22. Berdowska I. Cysteine proteases as disease markers. Clin. Chim. Acta. 2004; 342(1-2): 41-69.

Copyright (c) 2017 Eco-Vector


 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies