Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Dec;82(6):1915–1921. doi: 10.1172/JCI113810

L-428 nodular sclerosing Hodgkin's cell secretes a unique transforming growth factor-beta active at physiologic pH.

S R Newcom 1, M E Kadin 1, A A Ansari 1, V Diehl 1
PMCID: PMC442772  PMID: 2904450

Abstract

Nodular sclerosing Hodgkin's disease is characterized by dense collagen fibrosis. Although transforming growth factor-beta (TGF-beta) is an important bifunctional growth factor for fibroblasts and is stored and released by many cells, it requires acidification to pH 2.0-3.0 before it becomes a biologically active growth factor. We show here that the L-428 Hodgkin's cell releases a high molecular weight TGF that competes for the TGF-beta cell membrane receptor but not the TGF-alpha receptor. This growth factor is most active at physiologic pH and is 97% inactivated by acidification. Hodgkin's TGF is also inactivated by proteases and can be preserved by protease inhibitors. The Hodgkin's TGF can be separated from an autocrine growth factor using either column chromatography or electroelution from gels and is shown to have a molecular weight of approximately 350,000. Incubation of the Hodgkin's TGF in SDS releases a 25,000-D protein with reduced biological activity but which cross-reacts with anti-TGF-beta IgG. We propose that L-428 nodular sclerosing Hodgkin's disease fibrosis is mediated by a potent high molecular weight TGF-beta which, unlike TGF-beta characterized to date, is secreted in a form most active at physiologic pH.

Full text

PDF
1916

Images in this article

1917Image
on p.1917
1919Image
on p.1919
1919Image
on p.1919
1919Image
on p.1919

Selected References

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

  1. Assoian R. K., Komoriya A., Meyers C. A., Miller D. M., Sporn M. B. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed] [Google Scholar]
  2. Carr B. I., Hayashi I., Branum E. L., Moses H. L. Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type beta transforming growth factor. Cancer Res. 1986 May;46(5):2330–2334. [PubMed] [Google Scholar]
  3. Childs C. B., Proper J. A., Tucker R. F., Moses H. L. Serum contains a platelet-derived transforming growth factor. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5312–5316. doi: 10.1073/pnas.79.17.5312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  5. Diehl V., Kirchner H. H., Burrichter H., Stein H., Fonatsch C., Gerdes J., Schaadt M., Heit W., Uchanska-Ziegler B., Ziegler A. Characteristics of Hodgkin's disease-derived cell lines. Cancer Treat Rep. 1982 Apr;66(4):615–632. [PubMed] [Google Scholar]
  6. Falk M. H., Tesch H., Stein H., Diehl V., Jones D. B., Fonatsch C., Bornkamm G. W. Phenotype versus immunoglobulin and T-cell receptor genotype of Hodgkin-derived cell lines: activation of immature lymphoid cells in Hodgkin's disease. Int J Cancer. 1987 Aug 15;40(2):262–269. doi: 10.1002/ijc.2910400223. [DOI] [PubMed] [Google Scholar]
  7. Frolik C. A., Dart L. L., Meyers C. A., Smith D. M., Sporn M. B. Purification and initial characterization of a type beta transforming growth factor from human placenta. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3676–3680. doi: 10.1073/pnas.80.12.3676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frolik C. A., Wakefield L. M., Smith D. M., Sporn M. B. Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. J Biol Chem. 1984 Sep 10;259(17):10995–11000. [PubMed] [Google Scholar]
  9. Kadin M., Nasu K., Sako D., Said J., Vonderheid E. Lymphomatoid papulosis. A cutaneous proliferation of activated helper T cells expressing Hodgkin's disease-associated antigens. Am J Pathol. 1985 May;119(2):315–325. [PMC free article] [PubMed] [Google Scholar]
  10. Knabbe C., Lippman M. E., Wakefield L. M., Flanders K. C., Kasid A., Derynck R., Dickson R. B. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell. 1987 Feb 13;48(3):417–428. doi: 10.1016/0092-8674(87)90193-0. [DOI] [PubMed] [Google Scholar]
  11. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  12. Liu C., Tsao M. S., Grisham J. W. Transforming growth factors produced by normal and neoplastically transformed rat liver epithelial cells in culture. Cancer Res. 1988 Feb 15;48(4):850–855. [PubMed] [Google Scholar]
  13. Lukes R. J., Butler J. J. The pathology and nomenclature of Hodgkin's disease. Cancer Res. 1966 Jun;26(6):1063–1083. [PubMed] [Google Scholar]
  14. Massagué J., Like B. Cellular receptors for type beta transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines. J Biol Chem. 1985 Mar 10;260(5):2636–2645. [PubMed] [Google Scholar]
  15. Moses H. L., Branum E. L., Proper J. A., Robinson R. A. Transforming growth factor production by chemically transformed cells. Cancer Res. 1981 Jul;41(7):2842–2848. [PubMed] [Google Scholar]
  16. Muramoto L. M., Kadin M. E. Improved detection of lymphoid cell surface antigens in tissues fixed in periodate-lysine-paraformaldehyde (PLP). Am J Clin Pathol. 1987 Nov;88(5):589–595. doi: 10.1093/ajcp/88.5.589. [DOI] [PubMed] [Google Scholar]
  17. Mustoe T. A., Pierce G. F., Thomason A., Gramates P., Sporn M. B., Deuel T. F. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987 Sep 11;237(4820):1333–1336. doi: 10.1126/science.2442813. [DOI] [PubMed] [Google Scholar]
  18. Newcom S. R., O'Rourke L. Potentiation of fibroblast growth by nodular sclerosing Hodgkin's disease cell cultures. Blood. 1982 Jul;60(1):228–237. [PubMed] [Google Scholar]
  19. Newcom S. R. The Hodgkin's cell in nodular sclerosis does not release interleukin-1. J Lab Clin Med. 1985 Feb;105(2):170–177. [PubMed] [Google Scholar]
  20. Roberts A. B., Anzano M. A., Meyers C. A., Wideman J., Blacher R., Pan Y. C., Stein S., Lehrman S. R., Smith J. M., Lamb L. C. Purification and properties of a type beta transforming growth factor from bovine kidney. Biochemistry. 1983 Dec 6;22(25):5692–5698. doi: 10.1021/bi00294a002. [DOI] [PubMed] [Google Scholar]
  21. Roberts A. B., Anzano M. A., Wakefield L. M., Roche N. S., Stern D. F., Sporn M. B. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. doi: 10.1073/pnas.82.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roberts A. B., Frolik C. A., Anzano M. A., Sporn M. B. Transforming growth factors from neoplastic and nonneoplastic tissues. Fed Proc. 1983 Jun;42(9):2621–2626. [PubMed] [Google Scholar]
  23. Roberts A. B., Lamb L. C., Newton D. L., Sporn M. B., De Larco J. E., Todaro G. J. Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494–3498. doi: 10.1073/pnas.77.6.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schaadt M., Diehl V., Stein H., Fonatsch C., Kirchner H. H. Two neoplastic cell lines with unique features derived from Hodgkin's disease. Int J Cancer. 1980 Dec 15;26(6):723–731. doi: 10.1002/ijc.2910260605. [DOI] [PubMed] [Google Scholar]
  26. Sporn M. B., Roberts A. B., Wakefield L. M., Assoian R. K. Transforming growth factor-beta: biological function and chemical structure. Science. 1986 Aug 1;233(4763):532–534. doi: 10.1126/science.3487831. [DOI] [PubMed] [Google Scholar]
  27. Sundeen J., Lipford E., Uppenkamp M., Sussman E., Wahl L., Raffeld M., Cossman J. Rearranged antigen receptor genes in Hodgkin's disease. Blood. 1987 Jul;70(1):96–103. [PubMed] [Google Scholar]
  28. Tucker R. F., Branum E. L., Shipley G. D., Ryan R. J., Moses H. L. Specific binding to cultured cells of 125I-labeled type beta transforming growth factor from human platelets. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6757–6761. doi: 10.1073/pnas.81.21.6757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tucker R. F., Shipley G. D., Moses H. L., Holley R. W. Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science. 1984 Nov 9;226(4675):705–707. doi: 10.1126/science.6093254. [DOI] [PubMed] [Google Scholar]
  30. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES