Heterogeneity and basal autophagy in the cells of Hepatocarcinoma-29
DOI:
https://doi.org/10.26577/eb-2019-1-1398Abstract
The topic of research is the current direction of modern experimental oncology - the problem of studying the role of autophagy in the survival and death of a cancer cell. The purpose of this work was to study the cell heterogeneity of the hepatocarcinoma-29 population and the development of autophagy as a way of surviving tumor cells. The scientific
significance of the work lies in obtaining previously unknown facts about the development of basal autophagy in certain types of hepatocarcinoma cells, which is a way of surviving tumor cells. The novelty of this study is to identify the types of hepatocarcinoma cells in which the process of autophagy develops, contributing to the survival of the tumor cell population and obtaining data on the structural features and activity of the autophagy process.The practical significance of the work lies in the possibility of using the obtained data for the development of targeted therapy of hepatocarcinoma through the combined use of inducers of autophagy and cytostatics, which will simultaneously use different cellular signaling pathways to stimulate apoptosis and autophagic cell death. The work was performed on the culture of hepatocarcinoma -29 cells using light and electron microscopy. The heterogeneity of the population of cells was revealed, which is determined by the size of the cells and the volume fraction of the nucleus and cytoplasm. In terms of cell volume and nuclear-cytoplasmic ratio, five types of cells are distinguished, corresponding to five stages of differentiation. In the IV and V cells of the differentiation stages, autophagic structures were revealed: autophagosomes, autolysosomes, and lysosomes. The findings make a significant contribution to cell biology, cytology and histology, as well as oncology.
Key words: hepatocarcinoma-29, heterogeneity, stages of cell differentiation, autophag
References
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3. Wang K. Cancer stem cells of hepatocellular carcinoma. / K. Wang, D. Sun // Oncotarget – 2018. – № 9. – Vol. 33. – P. 23306–23314.
4. Thorburn A. Apoptosis and autophagy: regulatory connections between two supposedly different processes. / A. Thorburn // Apoptosis – 2008. – № 13. – Vol. 1. – P. 1–9.
5. Edinger A. L. Death by design: apoptosis, necrosis and autophagy. / A. L. Edinger, C. B. Thompson // Curr. Opin. Cell Biol. – 2004. – № 16. – Vol. 6. – P. 663–669.
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7. Cooper K. F. Till death do us part: the marriage of autophagy and apoptosis. // K. F. Cooper // Oxid. Med. Cell Longev. – 2018. – № 1. – Vol. 2. – P. 1–13.
8. Roy S. Autophagy and tumorigenesis. / S. Roy, J. Debnath // Semin. Immunopathol. – 2010. – № 32. – Vol. 4. – P. 383–96.
9. Parzych K. R. An overview of autophagy: morphology, mechanism, and regulation. / K. R. Parzych D. J. Klionsky // Antioxid. Redox. Signal. – 2014. – № 20. – Vol. 3. – P. 460–73.
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11. Каледин В.И., Жукова Н.А., Николин В.П. и др. Гепатокарцинома-29 – метастазирующая перевиваемая опухоль мышей, вызывающая кахексию // Бюл. эксперим. биол. мед. –2009. –Т. 148. № 12. – С. 664-669.
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14. Ravikumar B. Regulation of mammalian autophagy in physiology and pathophysiology. / B. Ravikumar, S. Sarkar, J. E. Davies, M. Futter, M. Garcia-Arencibia, Z. W. Green-Thompson et al. // Physiol. Rev. – 2010. – № 90. – Vol. 4. – P. 1383–435. 15. Nikoletopoulou V. Crosstalk between apoptosis, necrosis and autophagy. / V. Nikoletopoulou, M. Markaki, K. Palikaras, N. Tavernarakis // Biochim. Biophys. Acta – 2013. – № 1833. – Vol. 12. – P. 3448–3459.
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18. Yu L. Autophagy pathway: cellular and molecular mechanisms. / L. Yu, Y. Chen, S. A. Tooze // Autophagy – 2018. – № 14. – Vol. 2. – P. 207–215.
19. Yang Z. An overview of the molecular mechanism of autophagy. / Z. Yang, D. J. Klionsky // Curr. Top. Microbiol. Immunol. – 2009. – Vol. 335. – P. 1–32.
20. Suzuki H. Structural biology of the core autophagy machinery. / H. Suzuki, T. Osawa, Y. Fujioka, N. N. Noda // Curr. Opin. Struct. Biol. – 2017. – Vol. 43. – P. 10–17.
21. Ohsumi Y. Molecular dissection of autophagy: two ubiquitin-like systems. / Y. Ohsumi // Nat. Rev. Mol. Cell Biol. – 2001. – № 2. – Vol. 3. – P. 211–6.
22. Mercer T. J. A molecular perspective of mammalian autophagosome biogenesis. / T. J. Mercer, A. Gubas, S. A. Tooze // J. Biol. Chem. – 2018. – № 293. – Vol. 15. – P. 5386–5395 23. Balogh J. Hepatocellular carcinoma: a review. / J. Balogh, D. 3rd Victor, E. H. Asham, S. G. Burroughs, M. Boktour, A. Saharia et al. // J. Hepatocell. Carcinoma – 2016. – № 3. – Р.41–53.
24. Mazzanti R. Hepatocellular carcinoma: Where are we? / R. Mazzanti, U. Arena, R. Tassi // World J. Exp. Med. – 2016. – № 6. – Vol. 1. – P. 21–36.
25. Ковалева О.В., Шитова М.С., Зборовская И.Б.Аутофагия: клеточная гибельили способ выживания? //Клиническая онкогематология– 2014. – Т.7, №2, С. 103-114
26. Levine B., Klionsky D.J. Development by self-digestion: molecular mech-anisms and biological functions of autophagy. Dev. Cell 2004– Vol. 6(4)– P. 463–77.
27. He C., Klionsky D. J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. of Genet. – 2009.–.№ 6 – Vol.43.– P. 67–93.
28.Maycotte P., Thorburn A.. Autophagy and cancer therapy. Cancer Biol. – 2011–.№ 1 – Vol.11.– P. 127—137.
29. Hamacher-Brady A., Brady N. R., Gottlieb R. A.. The interplay between pro-death and prosurvival signaling pathways in myocardial ischemia/reperfusion injury: apoptosis meets autophagy. Cardiovasc. Drugs Ther. – 2006–.№ 6 – Vol.20.– P. 445–462.
30. Shay J. W., Roninson I. B. Hallmarks of senescence incarcinogenesis and cancer therapy. Oncogene. – 2004.–.№ 2– Vol.23.– P. 2919–2933.
31. Klionsky D. J., Cuervo A. M., Seglen P. O. Methods for mo-nitoring autophagy from yeast to human. Autophagy. – 2007 – №3– Vol.3.– P.181–206.
32. Kroemer G., Marino G., Levine B. Autophagy and theintegrated stress response. Mol. Cell. – 2010. – Vol.40.– P.280–293.
33. Mizushima N., Yamamoto A., Matsui M., Yoshimori T., Ohsu-mi Y.. In vivo analysis of autophagy in response to nutrientstarvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell. – 2004. – № 3–Vol.15.– P. 1101–1011.
34. Codogno P., Meijer A. J. Autophagy and signaling: theirrole in cell survival and cell death. Cell Death Differ. – 2005.– № 6 –Vol.12. – P. 1509– 1518.
35. Harrison D. E., Strong R., Sharp Z. D., Nelson J. F., Ast-le C. M., Flurkey K., Nadon N. L., Wilkinson J. E., Frenkel K., Carter C. S., Pahor M., Javors M. A., Fernandez E., Miller R. A. Rapamycin fed late in life extends lifespan in genetically heteroge-neous mice. Nature – 2009.– Vol. 460. – P. 392–395.
36. Okada H., Mak T.W. Pathways of apoptotic and non-apoptotic death intumor cells. Nat. Rev. Cancer – 2004.– Vol. 4(8). – P.592–603.
References
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3. Cui J. (2013) The role of autophagy in liver cancer: molecular mechanisms and potential therapeutic targets.J. Cui, Z. Gong, H. M. Shen.Biochim. Biophys. Acta., no.1836.,vol. 1.,pp.15–26.
4. Cooper K. F.( 2018) Till death do us part: the marriage of autophagy and apoptosis. K. F. Cooper. Oxid. Med. Cell Longev., no. 1, vol. 2, pp. 1–13.
5. Codogno P., Meijer A. J. (2005) Autophagy and signaling: theirrole in cell survival and cell death. Cell Death Differ. no.6, vol.12, pp. 1509– 1518.
6. Edinger A. L. (2004)Death by design: apoptosis, necrosis and autophagy. A. L. Edinger, C. B. Thompson Curr. Opin. Cell Biol. no.16, vol. 6, pp. 663–669. 7. Friemel J. (2015) Intratumor heterogeneity in hepatocellular carcinoma. J. Friemel, M. Rechsteiner, L. Frick, F. Böhm, K. Struckmann, M. Egger, H. Moch, M. Heikenwalder, A. Weber. Clin. Cancer Res. no. 21, vol. 8, pp. 1951–61.
8.He C., Klionsky D. J.( 2009) Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. of Genet. vol. 43, no 6, pp. 67-93.
9. Hamacher-Brady A., Brady N. R., Gottlieb R. A (2006) The interplay between prodeath and prosurvival signaling pathways in myocardial ischemia, reperfusion injury: apoptosis meets autophagy. Cardiovasc. Drugs Ther. vol. 20, no.6, pp. 445–462.
10. Harrison D. E., Strong R., Sharp Z. D., Nelson J. F., Ast-le C. M., Flurkey K., Nadon N. L., Wilkinson J. E., Frenkel K., Car-ter C. S., Pahor M., Javors M. A., Fernandez E., Miller R. A (2009) Rapamycin fed late in life extends lifespan in genetically heteroge-neous mice. Nature. vol. 460, pp. 392–395.
11.Kaledin V. I., Zhukova N. Ah. Nikolin V. P. et al. (2009) Hepatocarcinoma-29 is a metastatic transplantable tumor of mice causing cachexia. Bul. experiment. Biol. honey. vol. 148, no. 12, pp. 664-669.
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Published
2019-05-04
How to Cite
Dossymbekova, R. S., Tungushbaev, Z. B., Sharipov, K. O., Taskaev, Y. S., Solovieva, A. O., & Bgatova, N. P. (2019). Heterogeneity and basal autophagy in the cells of Hepatocarcinoma-29. Experimental Biology, 78(1), 140–150. https://doi.org/10.26577/eb-2019-1-1398
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HISTOLOGY
