Skip to main content
PMC home page
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
. 1988 Jun;85(12):4463–4467. doi: 10.1073/pnas.85.12.4463

Reversal of the metastatic phenotype in Lewis lung carcinoma cells after transfection with syngeneic H-2Kb gene.

D Plaksin 1, C Gelber 1, M Feldman 1, L Eisenbach 1
PMCID: PMC280450  PMID: 3380801

Abstract

High metastatic clones of the murine 3LL carcinoma express greatly reduced levels of H-2Kb major histocompatibility complex class I antigens, while low metastatic clones of the same tumor express high levels of H-2Kb. Induced expression of this antigen after transfection with the H-2Kb gene resulted in conversion of a metastatic to a non- or low-metastatic phenotype. Unlike the parental cells, transfected cells are potent inducers of H-2Kb-restricted syngeneic cytotoxic lymphocytes that kill the Kb-positive clones and cross-react with parental nontransfected cells. Preimmunization of mice with Kb-positive transfectants conferred protection against metastatic spread of malignant cells. Moreover, immunotherapy of metastasis was achieved by immunization with the H-2Kb-transfected cells of animals already carrying a growing local tumor of the parental cells.

Full text

PDF
4465

Images in this article

4464Image
on p.4464
4464Image
on p.4464

Selected References

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

  1. Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
  2. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  3. De Baetselier P., Katzav S., Gorelik E., Feldman M., Segal S. Differential expression of H-2 gene products in tumour cells in associated with their metastatogenic properties. Nature. 1980 Nov 13;288(5787):179–181. doi: 10.1038/288179a0. [DOI] [PubMed] [Google Scholar]
  4. Doyle A., Martin W. J., Funa K., Gazdar A., Carney D., Martin S. E., Linnoila I., Cuttitta F., Mulshine J., Bunn P. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. J Exp Med. 1985 May 1;161(5):1135–1151. doi: 10.1084/jem.161.5.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eisenbach L., Hollander N., Greenfeld L., Yakor H., Segal S., Feldman M. The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells. Int J Cancer. 1984 Oct 15;34(4):567–573. doi: 10.1002/ijc.2910340421. [DOI] [PubMed] [Google Scholar]
  6. Eisenbach L., Segal S., Feldman M. MHC imbalance and metastatic spread in Lewis lung carcinoma clones. Int J Cancer. 1983 Jul 15;32(1):113–120. doi: 10.1002/ijc.2910320118. [DOI] [PubMed] [Google Scholar]
  7. Festenstein H., Schmidt W. Variation in MHC antigenic profiles of tumor cells and its biological effects. Immunol Rev. 1981;60:85–127. doi: 10.1111/j.1600-065x.1981.tb00363.x. [DOI] [PubMed] [Google Scholar]
  8. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  9. Holden C. A., Sanderson A. R., MacDonald D. M. Absence of human leukocyte antigen molecules in skin tumors and some cutaneous appendages: evidence using monoclonal antibodies. J Am Acad Dermatol. 1983 Dec;9(6):867–871. doi: 10.1016/s0190-9622(83)70200-8. [DOI] [PubMed] [Google Scholar]
  10. Hui K., Grosveld F., Festenstein H. Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature. 1984 Oct 25;311(5988):750–752. doi: 10.1038/311750a0. [DOI] [PubMed] [Google Scholar]
  11. Isakov N., Feldman M., Segal S. Control of progression of local tumor and pulmonary metastasis of the 3LL Lewis lung carcinoma by different histocompatibility requirements in mice. J Natl Cancer Inst. 1981 May;66(5):919–926. [PubMed] [Google Scholar]
  12. Isakov N., Katzav S., Feldman M., Segal S. Loss of expression of transplantation antigens encoded by the H-2K locus on Lewis lung carcinoma cells and its relevance to the tumor's metastatic properties. J Natl Cancer Inst. 1983 Jul;71(1):139–145. [PubMed] [Google Scholar]
  13. Jacob F. Mouse teratocarcinoma and embryonic antigens. Immunol Rev. 1977 Jan;33:3–32. doi: 10.1111/j.1600-065x.1977.tb00360.x. [DOI] [PubMed] [Google Scholar]
  14. Katzav S., Segal S., Feldman M. Immuno-selection in vivo of H-2D phenotypic variants from a metastatic clone of sarcoma cells results in cell lines of altered metastatic competence. Int J Cancer. 1984 Mar 15;33(3):407–415. doi: 10.1002/ijc.2910330320. [DOI] [PubMed] [Google Scholar]
  15. Kress M., Glaros D., Khoury G., Jay G. Alternative RNA splicing in expression of the H-2K gene. Nature. 1983 Dec 8;306(5943):602–604. doi: 10.1038/306602a0. [DOI] [PubMed] [Google Scholar]
  16. Lalanne J. L., Delarbre C., Gachelin G., Kourilsky P. A cDNA clone containing the entire coding sequence of a mouse H-2Kd histocompatibility antigen. Nucleic Acids Res. 1983 Mar 11;11(5):1567–1577. doi: 10.1093/nar/11.5.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lampson L. A., Fisher C. A., Whelan J. P. Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines. J Immunol. 1983 May;130(5):2471–2478. [PubMed] [Google Scholar]
  18. Lew A. M., Margulies D. H., Maloy W. L., Lillehoj E. P., McCluskey J., Coligan J. E. Alternative protein products with different carboxyl termini from a single class I gene, H-2Kb. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6084–6088. doi: 10.1073/pnas.83.16.6084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Masucci M. G., Torsteindottir S., Colombani J., Brautbar C., Klein E., Klein G. Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4567–4571. doi: 10.1073/pnas.84.13.4567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  21. Rüsch E., Kuon W., Hämmerling G. J. Target sites for antibodies and cytotoxic T lymphocytes on H-2 molecules. Transplant Proc. 1983 Dec;15(4):2093–2096. [PubMed] [Google Scholar]
  22. Schmidt W., Festenstein H. Resistance to cell-mediated cytotoxicity is correlated with reduction of H-2K gene products in AKR leukemia. Immunogenetics. 1982;16(3):257–264. doi: 10.1007/BF00343314. [DOI] [PubMed] [Google Scholar]
  23. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  24. Shearer G. M., Schmitt-Verhulst A. M. Major histocompatibility complex restricted cell-mediated immunity. Adv Immunol. 1977;25:55–91. doi: 10.1016/s0065-2776(08)60931-1. [DOI] [PubMed] [Google Scholar]
  25. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  26. Tanaka K., Hayashi H., Hamada C., Khoury G., Jay G. Expression of major histocompatibility complex class I antigens as a strategy for the potentiation of immune recognition of tumor cells. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8723–8727. doi: 10.1073/pnas.83.22.8723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wallich R., Bulbuc N., Hämmerling G. J., Katzav S., Segal S., Feldman M. Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature. 1985 May 23;315(6017):301–305. doi: 10.1038/315301a0. [DOI] [PubMed] [Google Scholar]
  28. Weiss E., Golden L., Zakut R., Mellor A., Fahrner K., Kvist S., Flavell R. A. The DNA sequence of the H-2kb gene: evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibilty antigens. EMBO J. 1983;2(3):453–462. doi: 10.1002/j.1460-2075.1983.tb01444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [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