Plasminogen and PAI-1 activators in tissues of adenocarcinoma and squamous cell carcinoma of the esophagus


Cite item

Full Text

Abstract

Aim. The purpose of the study was to perform the comparative analysis of the components ofplasminogen activation system - uPA and tPA, and their inhibitor PAI-1 in tissues of esophageal adenocarcinoma (EA) and squamous cell carcinoma (SCC). Tissues of removed primary both EA (n=9, st II, G2, T2-3N0-1M0-1) and SCC (n=27, st II, G2, T2-3N0-1M0-1) were studied by ELISA. Results. EA and SCC tumor tissues showed a sharp increase in both uPA forms and in PAI-1, in EA tissue there was noted a decrease in all tPA and in SCC tissue there was seen a decline in tPA-act, compared to the resection line (RL). Perifocal zone of EA showed diminished uPA-Ag, all tPA, increased uPA-act and all PAI-1, compared to the RL. uPA and PAI-1 play an important role in progression of both SCC and EA. The role of tPA requires the further studying, but in SCC perifocal zone its impact may be rather harmful than protective. tPA-Ag/tPA-act balance was increased in SCC tissue only, while in other samples it was decreased (p<0.01) or had a clear tendency to decrease (p≤0.05), compared to RL area. Conclusions. 1. Concentrations of uPA-act and PAI-1 in tumors and surrounding tissues were significantly higher than in RL in both squamous cell carcinoma and adenocarcinoma; the imbalance between antigen and active uPA forms and PAI-1 was observed in all the cases. 2. tPA concentration was higher in adenocarcinoma RL than in tumor and its perifocal zone, while in perifocal zone of squamous cell carcinoma of the esophagus it was higher than in other tissue samples. 3. uPA, PAI-1 and probably tPA can become the targets for the therapy for esophageal squamous cell carcinoma and adenocarcinoma.

About the authors

O. I Kit

Rostov Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

E. N Kolesnikov

Rostov Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

E. M Frantsiyants

Rostov Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

Larisa S. Kozlova

Rostov Research Institute of Oncology

Email: 79094277471@yandex.ru
MD, PhD, associate professor, senior researcher of the hormonal laboratory Rostov-on-Don, 344037, Russian Federation

Yu. A Pogorelova

Rostov Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

N. D Cheryarina

Rostov Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

N. S Chugunova

Rostov Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

References

  1. Masson V. Roles of serine proteases and matrix metalloproteinases in tumor invasion and angiogenesis. Bull. Mem. Acad. Roy. Med. Belg. 2006; 161(5): 320-6.
  2. Айсина Р.Б., Мухаметова Л.И. Структура и функции системы плазминоге/плазмин. Биоорганическая химия. 2014; 40(6): 642-57. Review. Russian.
  3. Asuthkar S., Stepanova V., Lebedeva T., Holterman A.L., Estes N., Cines D.B. et al. Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer. Mol. Biol. Cell. 2013; 24(17): 2620-32.
  4. Witzel I., Milde-Langosch K., Schmidt M., Karn T., Becker S., Wirtz R. et al. Role of urokinase plasminogen activator and plasminogen activator inhibitor mRNA expression as prognostic factors in molecular subtypes of breast cancer. Onco Targets Ther. 2014; 7: 2205-13.
  5. Huang C., Xie D., Cui J., Li Q., Gao Y., Xie K. FOXM1c promotes pancreatic cancer epithelial-to-mesenchymal transition and metastasis via upregulation of expression of the urokinase plasminogen activator system. Clin. Cancer Res. 2014; 20(6): 1477-88.
  6. Gong L., Liu M., Zeng T., Shi X., Yuan C., Andreasen P.A. et al. Crystal structure of the Michaelis complex between tissue-type plasminogen activator and plasminogen activators inhibitor-1. J. Biol. Chem. 2015; 290(43): 25795-804.
  7. Jiang W.G., Sanders A.J., Katoh M., Ungefroren H. et al. Tissue invasion and metastasis: Molecular, biological and clinical perspectives. Semin. Cancer Biol. 2015; 244-75.
  8. McMahon B.J., Kwaan H.C. Components of the plasminogenplasmin system as biologic markers for cancer. Adv. Exp. Med. Biol. 2015; 867: 145-56.
  9. Fontanil T., Mohamedi Y., Esteban M.M., Obaya A.J., Cal S. Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA. Oncol. Rep. 2014; 31(6): 2792-6.
  10. Halámková J., Kiss I., Tomášek J., Pavlovský Z., Tuček S., Penka M. Significance of urokinase and its inhibitors in the invasiveness and metastasing of malignant tumors. Vnitr. Lek. 2012; 58(2): 129-34.
  11. Suh Y.S., Yu J., Kim B.C., Choi B., Han T.S., Ahn H.S. et al. Overexpression of plasminogen activator inhibitor-1 in advanced gastric cancer with aggressive lymph node metastasis. Cancer Res. Treat. 2015; 47(4): 718-26.
  12. Yamashita D., Kondo T., Ohue S., Takahashi H., Ishikawa M., Matoba R. et al. miR340 suppresses the stem-like cell function of glioma-initiating cells by targeting tissue plasminogen activator. Cancer Res. 2015; 75(6): 1123-33.
  13. Qureshi T., Goswami S., McClintock C.S., Ramsey M.T., Peterson C.B. Distinct encounter complexes of PAI-1 with plasminogen activators and vitronectin revealed by changes in the conformation and dynamics of the reactive center loop. Protein Sci. 2016; 25(2): 499-510.
  14. Iwaki T., Urano T., Umemura K. PAI-1, progress in understanding the clinical problem and its aetiology. Br. J. Haematol. 2012; 157(3): 291-8.
  15. Duffy M.J., McGowan P.M., Harbeck N., Thomssen C., Schmitt M. uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res. 2014; 16(4): 428.
  16. Chen H., Peng H., Liu W., Sun Y., Su N., Tang W. et al. Silencing of plasminogen activator inhibitor-1 suppresses colorectal cancer progression and liver metastasis. Surgery. 2015; 158(6): 1704-13.
  17. Кит О.И., Франциянц Е.М., Козлова Л.С., Терпугов А.Л. Серпины в гиперпластических тканях толстой кишки. Экспериментальная и клиническая гастроэнтерология. 2014; (10): 18-21.
  18. Кит О.И., Франциянц Е.М., Никипелова Е.А., Комарова Е.Ф., Козлова Л.С., Таварин И.С. и др. Изменения маркеров пролиферации, неоангиогенеза и системы активации плазминогена в ткани рака прямой кишки. Экспериментальная и клиническая гастроэнтерология. 2015, 114(2): 40-5.
  19. Козлова Л.С., Франциянц Е.М., Атмачиди Д.П., Горбунова Т.А. Ингибиторы протеолиза в ликворе больных злокачественными глиомами после двух видов локальной интраоперационной химиотерапии. Злокачественные опухоли. 2014; 3: 15-7.
  20. Lindahl T.L., Ohlsson P.I., Wiman B. The mechanism of the reaction between human plasminogen-activator inhibitor 1 and tissue plasminogen activator. Biochem. J. 1990; 265(1): 109-13.
  21. Suzuki Y., Mogami H., Ihara H., Urano T. Unique secretory dynamics of tissue plasminogen activator and its modulation by plasminogen activator inhibitor-1 in vascular endothelial cells. Blood. 2009; 113(2): 470-8.
  22. Suzuki Y., Urano T. Novel situations of endothelial injury in stroke-mechanisms of stroke and strategy of drug development: novel mechanism of the expression and amplification of cell surface-associated fibrinolytic activity demonstrated by real-time imaging analysis. J. Pharmacol. Sci. 2011; 116(1): 19-24.
  23. Niego B., Medcalf R.L. Plasmin-dependent modulation of the blood-brain barrier: a major consideration during tPA-induced thrombolysis? J. Cereb. Blood Flow. Metab. 2014; 34(8): 1283-96.
  24. Schuliga M. The inflammatory actions of coagulant and fibrinolytic proteases in disease. Mediat. Inflamm. 2015; 2015: 437695. doi : 10.1155/2015/437695. Review.

Copyright (c) 2016 Eco-Vector


 


This website uses cookies

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

About Cookies