Abstract
It has frequently been suggested that loss of beta 2-microglobulin (beta 2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of beta 2m expression in tumorigenicity. A beta 2 m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to beta 2 m expression. Transfection of an intact murine beta 2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4- 25- compared with beta 2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta 2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo.
Full Text
The Full Text of this article is available as a PDF (412.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bix M., Liao N. S., Zijlstra M., Loring J., Jaenisch R., Raulet D. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature. 1991 Jan 24;349(6307):329–331. doi: 10.1038/349329a0. [DOI] [PubMed] [Google Scholar]
- Elliott B. E., Carlow D. A., Rodricks A. M., Wade A. Perspectives on the role of MHC antigens in normal and malignant cell development. Adv Cancer Res. 1989;53:181–245. doi: 10.1016/s0065-230x(08)60282-1. [DOI] [PubMed] [Google Scholar]
- Gattoni-Celli S., Willett C. G., Rhoads D. B., Simon B., Strauss R. M., Kirsch K., Isselbacher K. J. Partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the H-2 class I gene H-2Ld into a human colon cancer cell line (HCT). Proc Natl Acad Sci U S A. 1988 Nov;85(22):8543–8547. doi: 10.1073/pnas.85.22.8543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Höglund P., Glas R., Ohlén C., Ljunggren H. G., Kärre K. Alteration of the natural killer repertoire in H-2 transgenic mice: specificity of rapid lymphoma cell clearance determined by the H-2 phenotype of the target. J Exp Med. 1991 Aug 1;174(2):327–334. doi: 10.1084/jem.174.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Höglund P., Ljunggren H. G., Ohlén C., Ahrlund-Richter L., Scangos G., Bieberich C., Jay G., Klein G., Kärre K. Natural resistance against lymphoma grafts conveyed by H-2Dd transgene to C57BL mice. J Exp Med. 1988 Oct 1;168(4):1469–1474. doi: 10.1084/jem.168.4.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
- Ljunggren H. G., Kärre K. Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J Exp Med. 1985 Dec 1;162(6):1745–1759. doi: 10.1084/jem.162.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ljunggren H. G., Kärre K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today. 1990 Jul;11(7):237–244. doi: 10.1016/0167-5699(90)90097-s. [DOI] [PubMed] [Google Scholar]
- Ljunggren H. G., Sturmhöfel K., Wolpert E., Hämmerling G. J., Kärre K. Transfection of beta 2-microglobulin restores IFN-mediated protection from natural killer cell lysis in YAC-1 lymphoma variants. J Immunol. 1990 Jul 1;145(1):380–386. [PubMed] [Google Scholar]
- Momburg F., Koch S. Selective loss of beta 2-microglobulin mRNA in human colon carcinoma. J Exp Med. 1989 Jan 1;169(1):309–314. doi: 10.1084/jem.169.1.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohlén C., Kling G., Höglund P., Hansson M., Scangos G., Bieberich C., Jay G., Kärre K. Prevention of allogeneic bone marrow graft rejection by H-2 transgene in donor mice. Science. 1989 Nov 3;246(4930):666–668. doi: 10.1126/science.2814488. [DOI] [PubMed] [Google Scholar]
- Ploegh H. L., Orr H. T., Strominger J. L. Major histocompatibility antigens: the human (HLA-A, -B, -C) and murine (H-2K, H-2D) class I molecules. Cell. 1981 May;24(2):287–299. doi: 10.1016/0092-8674(81)90318-4. [DOI] [PubMed] [Google Scholar]
- Seaman W. E., Sleisenger M., Eriksson E., Koo G. C. Depletion of natural killer cells in mice by monoclonal antibody to NK-1.1. Reduction in host defense against malignancy without loss of cellular or humoral immunity. J Immunol. 1987 Jun 15;138(12):4539–4544. [PubMed] [Google Scholar]
- Smith M. E. MHC antigen expression in colorectal tumours. Semin Cancer Biol. 1991 Feb;2(1):17–21. [PubMed] [Google Scholar]
- Sunday M. E., Isselbacher K. J., Gattoni-Celli S., Willett C. G. Altered growth of a human neuroendocrine carcinoma line after transfection of a major histocompatibility complex class I gene. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4700–4704. doi: 10.1073/pnas.86.12.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]