Skip to main content
SpringerLink
Log in

Autocrine Survival Factors of a Cytotoxic CTLL-2 Cell Line

  • Articles
  • Published:
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Cell survival in multicellular organisms is controlled by numerous cytokines, growth factors, and autocrine survival factors. Autocrine survival factors remain the least studied. The aim of this work was to study the autocrine factors which control survival of a CTLL-2 cytotoxic cell line: isolation and characterization of biologic activity along with physicochemical features of the active molecules have been performed. The conditioned medium of CTLL-2 cells containing autocrine factors was separated by gel filtration into four fractions: A, B, C, and D (according to the order of their efflux from the column). The biological activity of the fractions was tested by the MTT assay with the low density 5 days culture as a cell survival model. The testing of the ability of the fractions to support the cell survival in culture has shown that fractions A and B were active, whereas fractions C and D were not. The presence of a peptide of the molecular mass of 1157 Da in active fractions A and B has been detected by MALDI-TOF-mass-spectrometry. Considerable amount of lactate in fractions A and B, which flowed out from the column along with the peptide, has been detected with an enzymatic lactic acid assay. The lactate concentration in fraction A was 3.72 ± 0.11 mM and it was 0.83 ± 0.06 mM in fraction B. The obtained data suggest that fractions A and B contain supramolecular complexes of the peptide (M 1157 Da) with different lactate content. The peptide in a free form has not been found in the CTLL-2 cell conditioned medium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Raff M. C. 1992. Social controls on cell survival and cell death. Nature. 356, 397–400.

    Article  PubMed  CAS  Google Scholar 

  2. Ishizaki Y., Voyvodic J. T., Burne J. F., Raff M. C. 1993. Control of lens epithelial cell survival. J. Cell Biol. 121, 899–908.

    Article  PubMed  CAS  Google Scholar 

  3. Ishizaki Y., Burne J. F., Raff M. C. 1994. Autocrine signals enable chondrocytes to survive in culture. J. Cell Biol. 126, 1069–1077.

    Article  PubMed  CAS  Google Scholar 

  4. Ishizaki Y., Cheng L., Mudge A. W., Raff M. C. 1995. Programmed cell death by default in embryonic cells, fibroblasts, and cancer cells. Mol. Biol. Cell. 6, 1443–1458.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Stewart C. E., Rotwein P. 1996. Insulin-like growth factor-II is an autocrine survival factor for differentiating myoblasts. J. Biol. Chem. 271, 11330–11338.

    Article  PubMed  CAS  Google Scholar 

  6. Tamber A., Meikle M. C., Hill P. A. 2000. Autocrine signals promote osteoblast survival in culture. J. Endocrinol. 167, 383–390.

    Article  Google Scholar 

  7. Torcia M., Bracci-Laudiero L., Lucibello M., Nencioni L., Labardi D., Rubartelli A., Cozzolino F., Aloe L., Garaci E. 1996. Nerve growth factor is an autocrine survival factor for memory B lymphocytes. Cell. 85, 345–356.

    Article  PubMed  CAS  Google Scholar 

  8. Pincelli C., Haake A. R., Benassi L., Grassilli E., Magnoni C., Ottani D., Polakowska R., Franceschi C., Giannetti A. 1997. Autocrine nerve growth factor protects human keratinocytes from apoptosis through its high affinity receptor (TRK): A role for BCL-2. J. Invest. Dermatol. 109, 757–764.

    Article  PubMed  CAS  Google Scholar 

  9. Navarro-Tableros V., Sanchez-Soto M. C., Garcia S., Hiriart M. 2004. Autocrine regulation of single pancreatic β-cell survival. Diabetes. 53, 2018–2023.

    Article  PubMed  CAS  Google Scholar 

  10. Freedman M. H., Grunberger T., Correa P., Axelrad A. A., Dube I. D., Cohen A. 1993. Autocrine and paracrine growth control by granulocyte-monocyte colony-stimulation factor of acute lymphoblastic leukemia cells. Blood. 81, 3068–3075.

    PubMed  CAS  Google Scholar 

  11. Harris R. J., Pettitt A. R., Schmutz C., Sherrington P. D., Zuzel M., Cawley J. C., Griffiths S. D. 2000. Granulocyte-macrophage colony-stimulating factor as an autocrine survival factor for mature normal and malignant B lymphocytes. J. Immunol. 164, 3887–3893.

    Article  PubMed  CAS  Google Scholar 

  12. Gerber H. P., Malik A. K., Solar G. P., Sherman D., Liang X. H., Meng G., Hong K., Marsters J. C., Ferrara N. 2002. VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature. 417, 954–958.

    Article  PubMed  CAS  Google Scholar 

  13. Ogunshola O. O., Antic A., Donoghue M. J., Fan S. Y., Kim H., Stewart W. B., Madri J. A., Ment L. R. 2002. Paracrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system. J. Biol. Chem. 277, 11410–11415.

    Article  PubMed  CAS  Google Scholar 

  14. Bachelder R. E., Crago A., Chung J., Wendt M. A., Shaw L. M., Robinson G., Mercurio A. M. 2001. Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res. 61, 5736–5740.

    PubMed  CAS  Google Scholar 

  15. Ohmori H., Yamamoto I. 1987. β-Cyclodextrin as a substitude for fetal calf serum in the primary antibody response in vitro. Eur. J. Immunol. 17, 79–83.

    Article  PubMed  CAS  Google Scholar 

  16. Ohmori H. 1988. Development of a serum-free medium for in vitro immune responses by using β-cyclodextrin. J. Immunol. Meth. 112, 227–233.

    Article  CAS  Google Scholar 

  17. Denizot F., Lang R. 1986. Rapid colorimetric assay for cell growth and survival. J. Immunol. Meth. 82, 271–277.

    Article  Google Scholar 

  18. Rosenberg J. C., Rush B. F. 1966. An enzymatic-spectrophotometric determination of pyruvic and lactic acid in blood. Methodologic aspects. Clin. Chem. 12, 299–307.

    PubMed  CAS  Google Scholar 

  19. Lutsenko G. V., Grechikhina M. V., Dyachkova L. D. 2008. Autocrine factors in defense of cytotoxic CTLL-2 cells from oxidative stress. Cell and Tissue Biology. 2, 239–245.

    Article  Google Scholar 

  20. Lutsenko G. V., Grechikhina M. V., Dyachkova L. G., Sapozhnikov A. M. 2013. Protective effect of autocrine factors of cytotoxic T lymphocytes under conditions of chemical hypoxia. Immunologiya (Rus.). 34, 251–254.

    CAS  Google Scholar 

  21. Grechikhina M. V., Lutsenko G. V. 2014. Analysis of autocrine factors of cytotoxic T lymphocytes. Acta Naturae. Special Issue no. 1, 24.

    Google Scholar 

  22. Stid D. V., Atwood D. L. 2000. Supramolecular chemistry. NY: John Wiley & Sons Ltd, V. 1.

    Google Scholar 

  23. Halestrap A. P., Price N. T. 1999. The proton-linked monocarboxylate transporter (MCT) family: Structure, function and regulation. Biochem. J. 343, 281–299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Lutsenko G. V., Dyachkova L. G., Sapozhnikov A. M. 2001. Control of cell survival of a CTLL-2 cytotoxic cell line by autocrine factors. The role of the density of cell cultures. Biol. Membrany (Rus.). 18 (4), 312–319.

    CAS  Google Scholar 

  25. Lutsenko G. V., Dyachkova L. G. 2003. The role of energy metabolism of the cells of a cytotoxic CTLL-2 cell line in the mechanism of control of their survival by autocrine factors Biol. Membrany (Rus.). 20 (5), 401–408.

    CAS  Google Scholar 

  26. Lutsenko G. V., Grechikhina M. V., Dyachkova L. G. 2005. Regulation of the level of ATP in normal and transformed T cells by autocrine factors. Immunologiya (Rus.). 26 (2), 91–95.

    Google Scholar 

  27. Lutsenko G. V., Grechikhina M. V., Dyachkova L. G., Lutsan N. I. 2007. Effects of an autocrine factor deficit on the survival and energy metabolism of CTLL-2 cells under oxidative stress conditions in culture. Cell and Tissue Biology. 1, 235–243.

    Article  Google Scholar 

  28. Lutsenko G. V., Grechikhina M. V., Dyachkova L. G., Lutsan N. I. 2008. Survival of T lymphocytes under alkalosis and autocrine factor deficiency. Biochemistry (Moscow) Suppl. Series A: Membr. Cell Biol. 2, 318–325.

    Article  Google Scholar 

  29. Monteleon M., Stow J., Schroder K. 2015. Mechanisms of unconventional secretion of IL-1 family cytokines. Cytokine. 74 (2), 213–218.

    Article  CAS  Google Scholar 

  30. Steringer J. P., Muller H.-M., Nickel W. 2015. Unconventional secretion of fibroblast growth factor 2–a novel type of protein translocation across membranes? J. Mol. Biol. 427, 1202–1210.

    Article  CAS  Google Scholar 

  31. Tamkovich S. N., Tutanov O. S., Laktionov P. P. 2016. Exosomes: Mechanisms of origin, composition, transport, biological activity and use in diagnosis. Biol. Membrany (Rus.). 33 (3), 163–175.

    CAS  Google Scholar 

  32. Mause S. F., Weber C. 2010. Microparticles. Protagonists of a novel communication network for intercellular information exchange. Circ. Res. 107, 1047–1057.

    Article  PubMed  CAS  Google Scholar 

  33. Vincent A. M., Feldman E. L. 2002. Control of cell survival by IGF signaling pathways. Growth Horm. IGF Res. 12 (4), 193–197.

    Article  PubMed  CAS  Google Scholar 

  34. Proia P., Di Liegro C. M., Schiera G., Fricano A., Di Liegro I. 2016. Lactate as a metabolite and a regulator in the central nervous system. Int. J. Mol. Sci. 17 (9), 234–241.

    Article  CAS  Google Scholar 

  35. Rooney K., Trayhurn P. 2011. Lactate and the GPR81 receptor in metabolic regulation: Implications for adipose tissue function and fatty acid utilisation by muscle during exercise. Br. J. Nutr. 106 (9), 1310–1316.

    Article  PubMed  CAS  Google Scholar 

  36. Roland C. L., Arumugam T., Deng D., Liu S. H., Philip B., Gomez S., Burns W. R., Ramachandran V., Wang H., Cruz-Monserrate Z., Logsdon C. D. 2014. Cell surface lactate receptor GPR81 is crucial for cancer cell survival. Cancer Res. 74 (18), 5301–5310.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Shemiakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia

    G. V. Lutsenko, M. V. Grechikhina & M. A. Efremov

Authors
  1. G. V. Lutsenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Grechikhina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. A. Efremov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. V. Lutsenko.

Additional information

Original Russian Text © G.V. Lutsenko, M.V. Grechikhina, M.A. Efremov, 2018, published in Biologicheskie Membrany, 2018, Vol. 35, No. 4, pp. 271–279.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lutsenko, G.V., Grechikhina, M.V. & Efremov, M.A. Autocrine Survival Factors of a Cytotoxic CTLL-2 Cell Line. Biochem. Moscow Suppl. Ser. A 12, 239–246 (2018). https://doi.org/10.1134/S1990747818030066

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990747818030066

Keywords

Search

Navigation