Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Oct;82(20):6932–6936. doi: 10.1073/pnas.82.20.6932

Autocrine growth stimulation of a human T-cell lymphoma line by interleukin 2.

V Duprez, G Lenoir, A Dautry-Varsat
PMCID: PMC390802  PMID: 3931081

Abstract

The ability of tumor cells to produce and to respond to their own growth factor (autocrine secretion) may be of importance for their growth. We describe a human tumor cell line regulated by an autocrine secretion of the growth factor interleukin 2 (IL-2). This T-lymphocyte cell line, IARC 301, was established from a patient with a T-cell lymphoma in the absence of any added specific growth factor. It constitutively expresses biologically functional high-affinity cell-surface receptors for IL-2 as shown by the binding of both radiolabeled purified IL-2 and monoclonal antibodies to IL-2 receptors. In addition, it synthesizes IL-2, which is bound to cell surface receptors. Monoclonal antibodies directed against either IL-2 or the IL-2 receptor block IARC 301 cell growth. These findings demonstrate that the proliferation of this tumor cell line is mediated by an autocrine pathway involving endogenous IL-2 production and its binding to cell surface receptors.

Full text

PDF
6932

Selected References

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

  1. Adkins B., Leutz A., Graf T. Autocrine growth induced by src-related oncogenes in transformed chicken myeloid cells. Cell. 1984 Dec;39(3 Pt 2):439–445. doi: 10.1016/0092-8674(84)90451-3. [DOI] [PubMed] [Google Scholar]
  2. Arya S. K., Wong-Staal F., Gallo R. C. T-cell growth factor gene: lack of expression in human T-cell leukemia-lymphoma virus-infected cells. Science. 1984 Mar 9;223(4640):1086–1087. doi: 10.1126/science.6320374. [DOI] [PubMed] [Google Scholar]
  3. Baker P. E., Gillis S., Smith K. A. Monoclonal cytolytic T-cell lines. J Exp Med. 1979 Jan 1;149(1):273–278. doi: 10.1084/jem.149.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Betsholtz C., Westermark B., Ek B., Heldin C. H. Coexpression of a PDGF-like growth factor and PDGF receptors in a human osteosarcoma cell line: implications for autocrine receptor activation. Cell. 1984 Dec;39(3 Pt 2):447–457. doi: 10.1016/0092-8674(84)90452-5. [DOI] [PubMed] [Google Scholar]
  5. Cantrell D. A., Smith K. A. The interleukin-2 T-cell system: a new cell growth model. Science. 1984 Jun 22;224(4655):1312–1316. doi: 10.1126/science.6427923. [DOI] [PubMed] [Google Scholar]
  6. Cantrell D. A., Smith K. A. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983 Dec 1;158(6):1895–1911. doi: 10.1084/jem.158.6.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clark S. C., Arya S. K., Wong-Staal F., Matsumoto-Kobayashi M., Kay R. M., Kaufman R. J., Brown E. L., Shoemaker C., Copeland T., Oroszlan S. Human T-cell growth factor: partial amino acid sequence, cDNA cloning, and organization and expression in normal and leukemic cells. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2543–2547. doi: 10.1073/pnas.81.8.2543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  9. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  10. Ehrlich R., Witz I. P. The elution of antibodies from viable murine tumor cells. J Immunol Methods. 1979;26(4):345–353. doi: 10.1016/0022-1759(79)90180-7. [DOI] [PubMed] [Google Scholar]
  11. Garrett J. S., Coughlin S. R., Niman H. L., Tremble P. M., Giels G. M., Williams L. T. Blockade of autocrine stimulation in simian sarcoma virus-transformed cells reverses down-regulation of platelet-derived growth factor receptors. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7466–7470. doi: 10.1073/pnas.81.23.7466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  13. Gootenberg J. E., Ruscetti F. W., Mier J. W., Gazdar A., Gallo R. C. Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor. J Exp Med. 1981 Nov 1;154(5):1403–1418. doi: 10.1084/jem.154.5.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hemler M. E., Brenner M. B., McLean J. M., Strominger J. L. Antigenic stimulation regulates the level of expression of interleukin 2 receptor on human T cells. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2172–2175. doi: 10.1073/pnas.81.7.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hemler M. E., Malissen B., Rebai N., Liabeuf A., Mawas C., Kourilsky F. M., Strominger J. L. A 55,000 Mr surface antigen on activated human T lymphocytes defined by a monoclonal antibody. Hum Immunol. 1983 Oct;8(2):153–165. doi: 10.1016/0198-8859(83)90010-1. [DOI] [PubMed] [Google Scholar]
  16. Huang J. S., Huang S. S., Deuel T. F. Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Cell. 1984 Nov;39(1):79–87. doi: 10.1016/0092-8674(84)90193-4. [DOI] [PubMed] [Google Scholar]
  17. Kaplan D. R., Braciale V. L., Braciale T. J. Antigen-dependent regulation of interleukin 2 receptor expression on cloned human cytotoxic T lymphocytes. J Immunol. 1984 Oct;133(4):1966–1969. [PubMed] [Google Scholar]
  18. Kaplan P. L., Topp W. C., Ozanne B. Simian virus 40 induces the production of a polypeptide transforming factor(s). Virology. 1981 Jan 30;108(2):484–490. doi: 10.1016/0042-6822(81)90455-4. [DOI] [PubMed] [Google Scholar]
  19. Leonard W. J., Depper J. M., Uchiyama T., Smith K. A., Waldmann T. A., Greene W. C. A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982 Nov 18;300(5889):267–269. doi: 10.1038/300267a0. [DOI] [PubMed] [Google Scholar]
  20. Meuer S. C., Hussey R. E., Cantrell D. A., Hodgdon J. C., Schlossman S. F., Smith K. A., Reinherz E. L. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. doi: 10.1073/pnas.81.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  22. Ozanne B., Fulton R. J., Kaplan P. L. Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell-line produce transforming factors. J Cell Physiol. 1980 Oct;105(1):163–180. doi: 10.1002/jcp.1041050118. [DOI] [PubMed] [Google Scholar]
  23. Robb R. J., Greene W. C. Direct demonstration of the identity of T cell growth factor binding protein and the Tac antigen. J Exp Med. 1983 Oct 1;158(4):1332–1337. doi: 10.1084/jem.158.4.1332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Robb R. J., Greene W. C., Rusk C. M. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med. 1984 Oct 1;160(4):1126–1146. doi: 10.1084/jem.160.4.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rosenberg S. A., Grimm E. A., McGrogan M., Doyle M., Kawasaki E., Koths K., Mark D. F. Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science. 1984 Mar 30;223(4643):1412–1414. doi: 10.1126/science.6367046. [DOI] [PubMed] [Google Scholar]
  27. Smith K. A., Favata M. F., Oroszlan S. Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics. J Immunol. 1983 Oct;131(4):1808–1815. [PubMed] [Google Scholar]
  28. Smith K. A. Interleukin 2. Annu Rev Immunol. 1984;2:319–333. doi: 10.1146/annurev.iy.02.040184.001535. [DOI] [PubMed] [Google Scholar]
  29. Smith K. A. T-cell growth factor and glucocorticoids: opposing regulatory hormones in neoplastic T-cell growth. Immunobiology. 1982 Mar;161(1-2):157–173. doi: 10.1016/S0171-2985(82)80023-5. [DOI] [PubMed] [Google Scholar]
  30. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  31. Taniguchi T., Matsui H., Fujita T., Takaoka C., Kashima N., Yoshimoto R., Hamuro J. Structure and expression of a cloned cDNA for human interleukin-2. Nature. 1983 Mar 24;302(5906):305–310. doi: 10.1038/302305a0. [DOI] [PubMed] [Google Scholar]
  32. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  33. Ullrich A., Coussens L., Hayflick J. S., Dull T. J., Gray A., Tam A. W., Lee J., Yarden Y., Libermann T. A., Schlessinger J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. 1984 May 31-Jun 6Nature. 309(5967):418–425. doi: 10.1038/309418a0. [DOI] [PubMed] [Google Scholar]
  34. Vodinelich L., Tax W., Bai Y., Pegram S., Capel P., Greaves M. F. A monoclonal antibody (WT1) for detecting leukemias of T-cell precursors (T-ALL). Blood. 1983 Nov;62(5):1108–1113. [PubMed] [Google Scholar]
  35. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  36. 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 Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES