Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1988 Sep;58(3):306–313. doi: 10.1038/bjc.1988.209

Relationship between changes in antigen expression and protein synthesis in human melanoma cells after hyperthermia and photodynamic treatment.

C L Davies 1, T Ranheim 1, Z Malik 1, E K Rofstad 1, J Moan 1, T Lindmo 1
PMCID: PMC2246583  PMID: 3179182

Abstract

Hyperthermia and photoactivated hematoporphyrin derivative induce a dose-dependent reduction in the expression of the p250 surface melanoma-associated antigen on the human FME cell line. Expression of this glycoprotein antigen was quantitated by immunofluorescence flow cytometry based on the monoclonal antibody 9.2.27. Decrease in antigen expression was followed by a transient increase above the level for untreated cells, before normalization occurred about one week after treatment. These treatment-induced changes in antigen expression could partly be explained by changes in protein synthesis. This conclusion was based on the following observations: Hyperthermia and photoactivated hematoporphyrin derivative both inhibited protein synthesis. The latter increased again rapidly to rates above normal until antigen expression reached normal level, whereupon the protein synthesis rate decreased to normal. Inhibition of protein synthesis by cycloheximide 1 day after heating, prevented the recovery of antigen expression, demonstrating that protein synthesis is necessary for resumption of normal antigen expression. The changes in both antigen expression and protein synthesis were dose-dependent, and the magnitude and duration of the changes increased with increasing dose. The time courses of the changes in protein synthesis after two different treatments which both inactivated two logs of cells were almost identical, as were the time courses after two lower heat doses inactivating one log of cells. These similarities were reflected in the changes in antigen expression. At the same time as protein synthesis reached its maximum and antigen expression resumed normal level, an increase in the Golgi apparatus was observed ultrastructurally, indicating an increased synthesis rate and transportation of glycoproteins to the cell surface.

Full text

PDF
306

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bellnier D. A., Dougherty T. J. Membrane lysis in Chinese hamster ovary cells treated with hemtoporphyrin derivative plus light. Photochem Photobiol. 1982 Jul;36(1):43–47. doi: 10.1111/j.1751-1097.1982.tb04338.x. [DOI] [PubMed] [Google Scholar]
  2. Bleiberg I., Sohar E. The effect of heat treatment on the damage and recovery of the protein synthesis mechanism of human kidney cell line. Virchows Arch B Cell Pathol. 1975;17(3):269–278. doi: 10.1007/BF02912854. [DOI] [PubMed] [Google Scholar]
  3. Bumol T. F., Reisfeld R. A. Unique glycoprotein-proteoglycan complex defined by monoclonal antibody on human melanoma cells. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1245–1249. doi: 10.1073/pnas.79.4.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bumol T. F., Walker L. E., Reisfeld R. A. Biosynthetic studies of proteoglycans in human melanoma cells with a monoclonal antibody to a core glycoprotein of chondroitin sulfate proteoglycans. J Biol Chem. 1984 Oct 25;259(20):12733–12741. [PubMed] [Google Scholar]
  5. Chakrabarty S., McRae L. J., Levine A. E., Brattain M. G. Restoration of normal growth control and membrane antigen composition in malignant cells by N,N-dimethylformamide. Cancer Res. 1984 May;44(5):2181–2185. [PubMed] [Google Scholar]
  6. Christensen T., Sandquist T., Feren K., Waksvik H., Moan J. Retention and photodynamic effects of haematoporphyrin derivative in cells after prolonged cultivation in the presence of porphyrin. Br J Cancer. 1983 Jul;48(1):35–43. doi: 10.1038/bjc.1983.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davies C. D., Western A., Lindmo T., Moan J. Changes in antigen expression on human FME melanoma cells after exposure to photoactivated hematoporphyrin derivative. Cancer Res. 1986 Dec;46(12 Pt 1):6068–6072. [PubMed] [Google Scholar]
  8. Davies C. de L., Rofstad E. K., Lindmo T. Hyperthermia-induced changes in antigen expression on human FME melanoma cells. Cancer Res. 1985 Sep;45(9):4109–4114. [PubMed] [Google Scholar]
  9. Dewey W. C., Hopwood L. E., Sapareto S. A., Gerweck L. E. Cellular responses to combinations of hyperthermia and radiation. Radiology. 1977 May;123(2):463–474. doi: 10.1148/123.2.463. [DOI] [PubMed] [Google Scholar]
  10. Dickson J. A., Shah D. M. The effects of hyperthermia (42 degrees C) on the biochemistry and growth of a malignant cell line. Eur J Cancer. 1972 Oct;8(5):561–571. doi: 10.1016/0014-2964(72)90110-7. [DOI] [PubMed] [Google Scholar]
  11. Fritsch P., Gschnait F., Hönigsmann H., Wolff K. Protective action of beta-carotene against lethal photosensitization of fibroblasts in vitro. Br J Dermatol. 1976 Mar;94(3):263–271. doi: 10.1111/j.1365-2133.1976.tb04382.x. [DOI] [PubMed] [Google Scholar]
  12. Fuhr J. E. Effect of hyperthermia on protein biosynthesis in L5178Y murine leukemic lymphoblasts. J Cell Physiol. 1974 Dec;84(3):365–372. doi: 10.1002/jcp.1040840305. [DOI] [PubMed] [Google Scholar]
  13. Giovanella B. C., Lohman W. A., Heidelberger C. Effects of elevated temperatures and drugs on the viability of L1210 leukemia cells. Cancer Res. 1970 Jun;30(6):1623–1631. [PubMed] [Google Scholar]
  14. Girotti A. W., Deziel M. R. Photodynamic action of protoporphyrin on resealed erythrocyte membranes: mechanisms of release of trapped markers. Adv Exp Med Biol. 1983;160:213–225. doi: 10.1007/978-1-4684-4406-3_19. [DOI] [PubMed] [Google Scholar]
  15. Hahn G. M., Shiu E. C. Protein synthesis, thermotolerance and step down heating. Int J Radiat Oncol Biol Phys. 1985 Jan;11(1):159–164. doi: 10.1016/0360-3016(85)90375-x. [DOI] [PubMed] [Google Scholar]
  16. Henle K. J., Leeper D. B. Effects of hyperthermia (45 degrees) on macromolecular synthesis in Chinese hamster ovary cells. Cancer Res. 1979 Jul;39(7 Pt 1):2665–2674. [PubMed] [Google Scholar]
  17. Kessel D. Effects of photoactivated porphyrins at the cell surface of leukemia L1210 cells. Biochemistry. 1977 Jul 26;16(15):3443–3449. doi: 10.1021/bi00634a023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kessel D. Transport and binding of hematoporphyrin derivative and related porphyrins by murine leukemia L1210 cells. Cancer Res. 1981 Apr;41(4):1318–1323. [PubMed] [Google Scholar]
  19. LIPSON R. L., BALDES E. J., OLSEN A. M. The use of a derivative of hematoporhyrin in tumor detection. J Natl Cancer Inst. 1961 Jan;26:1–11. [PubMed] [Google Scholar]
  20. Leibson P. J., Schreiber H., Loken M. R., Panem S., Rowley D. A. Time-dependent resistance or susceptibility of tumor cells to cytotoxic antibody after exposure to a chemotherapeutic agent. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6202–6206. doi: 10.1073/pnas.75.12.6202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lepock J. R. Involvement of membranes in cellular responses to hyperthermia. Radiat Res. 1982 Dec;92(3):433–438. [PubMed] [Google Scholar]
  22. Lin G. S., Al-Dakan A. A., Gibson D. P. Inhibition of DNA and protein synthesis and cell division by photoactivated haematoporphyrin derivative in hamster ovary cells. Br J Cancer. 1986 Feb;53(2):265–269. doi: 10.1038/bjc.1986.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lindmo T., Davies C., Fodstad O., Morgan A. C. Stable quantitative differences of antigen expression in human melanoma cells isolated by flow cytometric cell sorting. Int J Cancer. 1984 Oct 15;34(4):507–512. doi: 10.1002/ijc.2910340413. [DOI] [PubMed] [Google Scholar]
  24. Lindmo T., Davies C., Rofstad E. K., Fodstad O., Sundan A. Antigen expression in human melanoma cells in relation to growth conditions and cell-cycle distribution. Int J Cancer. 1984 Feb 15;33(2):167–171. doi: 10.1002/ijc.2910330203. [DOI] [PubMed] [Google Scholar]
  25. McCormick W., Penman S. Regulation of protein synthesis in HeLa cells: translation at elevated temperatures. J Mol Biol. 1969 Jan;39(2):315–333. doi: 10.1016/0022-2836(69)90320-9. [DOI] [PubMed] [Google Scholar]
  26. Mitranic M., Sturgess J. M., Moscarello M. A. The effect of temperature on the galactosyl- and sialyltransferases and on the ultrastructure of Golgi membranes. Biochim Biophys Acta. 1976 Aug 16;443(2):190–197. doi: 10.1016/0005-2736(76)90502-2. [DOI] [PubMed] [Google Scholar]
  27. Moan J. Effect of bleaching of porphyrin sensitizers during photodynamic therapy. Cancer Lett. 1986 Oct;33(1):45–53. doi: 10.1016/0304-3835(86)90100-x. [DOI] [PubMed] [Google Scholar]
  28. Moan J., McGhie J., Jacobsen P. B. Photodynamic effects on cells in vitro exposed to hematoporphyrin derivative and light. Photochem Photobiol. 1983 Jun;37(6):599–604. doi: 10.1111/j.1751-1097.1983.tb04527.x. [DOI] [PubMed] [Google Scholar]
  29. Moan J., Vistnes A. I. Porphyrin photosensitization of proteins in cell membranes as studied by spin-labelling and by quantification of DTNB-reactive SH-groups. Photochem Photobiol. 1986 Jul;44(1):15–19. doi: 10.1111/j.1751-1097.1986.tb03558.x. [DOI] [PubMed] [Google Scholar]
  30. Mondovì B., Finazzi Agrò A., Rotilio G., Strom R., Moricca G., Rossi Fanelli A. The biochemical mechanism of selective heat sensitivity of cancer cells. II. Studies on nucleic acids and protein synthesis. Eur J Cancer. 1969 May;5(2):137–146. doi: 10.1016/0014-2964(69)90060-7. [DOI] [PubMed] [Google Scholar]
  31. Rønning O. W., Pettersen E. O., Seglen P. O. Protein synthesis and protein degradation through the cell cycle of human NHIK 3025 cells in vitro. Exp Cell Res. 1979 Oct 1;123(1):63–72. doi: 10.1016/0014-4827(79)90421-x. [DOI] [PubMed] [Google Scholar]
  32. Seglen P. O., Solheim A. E. Valine uptake and incorporation into protein in isolated rat hepatocytes. Nature of the precursor pool for protein synthesis. Eur J Biochem. 1978 Apr;85(1):15–25. doi: 10.1111/j.1432-1033.1978.tb12208.x. [DOI] [PubMed] [Google Scholar]
  33. Shapiro S. J., Leibson P. J., Loken M. R., Schreiber H. Changes in susceptibility to cytotoxic antibody among tumor cells surviving exposure to chemotherapeutic agents. Cancer Res. 1982 Jul;42(7):2622–2627. [PubMed] [Google Scholar]
  34. Tompkins W. A., Rama Rao G. V., Pantasatos P., Cain C. A. Hyperthermia enhancement of antibody-complement cytotoxicity for human colon tumor cells. J Natl Cancer Inst. 1981 Mar;66(3):453–459. [PubMed] [Google Scholar]
  35. Tveit K. M., Fodstad O., Johannessen J. V., Olsnes S. A human melanoma cell line established from xenograft in athymic mice. Br J Cancer. 1980 May;41(5):724–733. doi: 10.1038/bjc.1980.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Westra A., Dewey W. C. Variation in sensitivity to heat shock during the cell-cycle of Chinese hamster cells in vitro. Int J Radiat Biol Relat Stud Phys Chem Med. 1971;19(5):467–477. doi: 10.1080/09553007114550601. [DOI] [PubMed] [Google Scholar]
  37. van Steveninck J., Dubbelman T. M., Verweij H. Photodynamic membrane damage. Adv Exp Med Biol. 1983;160:227–240. doi: 10.1007/978-1-4684-4406-3_20. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES