Abstract
We have shown that both regressor and progressor clones can be isolated from a UV regressor tumor, RD-1024. Although the daughter clones are characterized by differences in tumorigenic potential in normal transplant hosts, they nevertheless seem to express the same major tumor rejection antigens, because immunization with either the regressor parent tumor, RD-1024, or with regressor Cl 8 protects against subsequent challenge with progressor C1 4 or Cl 9. Consistent with the in vivo-generated data is the evidence that draining lymph node cells with functional specificity for regressor Cl 8 are capable of cross-reactive cytotoxicity in an in vitro chromium release assay. We have demonstrated an indirect interaction occurring in vivo between regressor and progressor cells, in that Cl 8 cells have the ability to influence the outcome of simultaneous or sequential challenge with Cl 4 or Cl 9 cells. Because 500 rad of gamma irradiation has been shown to compromise the ability of mice to respond to a primary challenge with tumor, an immunological mechanism is implicated in the ultimate rejection of progressor tumor in a doubly challenged host. The importance of these results lies in the knowledge that these interacting subpopulations have been isolated directly from a tumor growing in vivo and that no selection pressure has been exerted on the cells greater than the short in vitro culture period necessary for the isolation and expansion of individual clones. The apparent immunoregulatory potential in a tumor-bearing animal is thus seen to be modified in accordance with the phenotypic heterogeneity of the cells within that tumor.
Full Text
The Full Text of this article is available as a PDF (909.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Becker F. F., Klein K. M., Wolman S. R., Asofsky R., Sell S. Characterization of primary hepatocellular carcinomas and initial transplant generations. Cancer Res. 1973 Dec;33(12):3330–3338. [PubMed] [Google Scholar]
- Boon T., Kellermann O. Rejection by syngeneic mice of cell variants obtained by mutagenesis of a malignant teratocarcinoma cell line. Proc Natl Acad Sci U S A. 1977 Jan;74(1):272–275. doi: 10.1073/pnas.74.1.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coggin J. H., Jr, Anderson N. G. Cancer, differentiation and embryonic antigens: some central problems. Adv Cancer Res. 1974;19(0):105–165. doi: 10.1016/s0065-230x(08)60053-6. [DOI] [PubMed] [Google Scholar]
- Daynes R. A., Spellman C. W., Woodward J. G., Stewart D. A. Studies into the transplantation biology of ultraviolet light-induced tumors. Transplantation. 1977 Apr;23(4):343–348. doi: 10.1097/00007890-197704000-00008. [DOI] [PubMed] [Google Scholar]
- Dexter D. L., Kowalski H. M., Blazar B. A., Fligiel Z., Vogel R., Heppner G. H. Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Res. 1978 Oct;38(10):3174–3181. [PubMed] [Google Scholar]
- Freedman V. H., Shin S. I. Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell. 1974 Dec;3(4):355–359. doi: 10.1016/0092-8674(74)90050-6. [DOI] [PubMed] [Google Scholar]
- HENDERSON J. S., ROUS P. The plating of tumor components on the subcutaneous expanses of young mice. Findings with benign and malignant epidermal growths and with mammary carcinomas. J Exp Med. 1962 Jun 1;115:1211–1230. doi: 10.1084/jem.115.6.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heppner G. H., Dexter D. L., DeNucci T., Miller F. R., Calabresi P. Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor. Cancer Res. 1978 Nov;38(11 Pt 1):3758–3763. [PubMed] [Google Scholar]
- Kripke M. L. Antigenicity of murine skin tumors induced by ultraviolet light. J Natl Cancer Inst. 1974 Nov;53(5):1333–1336. doi: 10.1093/jnci/53.5.1333. [DOI] [PubMed] [Google Scholar]
- Kripke M. L., Gruys E., Fidler I. J. Metastatic heterogeneity of cells from an ultraviolet light-induced murine fibrosarcoma of recent origin. Cancer Res. 1978 Sep;38(9):2962–2967. [PubMed] [Google Scholar]
- LAW L. W. Origin of the resistance of leukaemic cells to folic acid antagonists. Nature. 1952 Apr 12;169(4302):628–629. doi: 10.1038/169628a0. [DOI] [PubMed] [Google Scholar]
- Mitelman F. The chromosomes of fifty primary Rous rat sarcomas. Hereditas. 1971;69(2):155–186. doi: 10.1111/j.1601-5223.1971.tb02431.x. [DOI] [PubMed] [Google Scholar]
- Parmiani G., Invernizzi G. Alien histocompatibility determinants on the cell surface of sarcomas induced by methylcholanthrene. I. In vivo studies. Int J Cancer. 1975 Nov 15;16(5):756–767. doi: 10.1002/ijc.2910160508. [DOI] [PubMed] [Google Scholar]
- Patek P. Q., Collins J. L., Cohn M. Transformed cell lines susceptible or resistant to in vivo surveillance against tumorigenesis. Nature. 1978 Nov 30;276(5687):510–511. doi: 10.1038/276510a0. [DOI] [PubMed] [Google Scholar]
- Schabel F. M., Jr Concepts for systemic treatment of micrometastases. Cancer. 1975 Jan;35(1):15–24. doi: 10.1002/1097-0142(197501)35:1<15::aid-cncr2820350104>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
- Sluyser M., Van Nie R. Estrogen receptor content and hormone-responsive growth of mouse mammary tumors. Cancer Res. 1974 Dec;34(12):3253–3257. [PubMed] [Google Scholar]
- Spellman C. W., Daynes R. A. Ultraviolet light induced murine suppressor lymphocytes dictate specificity of anti-ultraviolet tumor immune responses. Cell Immunol. 1978 Jun;38(1):25–34. doi: 10.1016/0008-8749(78)90028-x. [DOI] [PubMed] [Google Scholar]