Abstract
The cells of a mouse mammary cancer were obtained with enzymes in suspensions which could be filtered to exclude all which were not single and most which were already dead. Heavy suspensions of these individual cells were plated over the dorsal subcutaneous expanses of female weanling mice where they implanted and grew to form coalescent tumors covering the back more or less entirely. Sparser suspensions, similarly plated (a) gave rise to fewer tumors, and (b) gave rise to tumors reaching measurable size later. These two consequences of sparser plating left room for the testing of adjuvators to transplantation. Adjuvator effects were obtained by splitting the subcutaneous expanses beforehand and by injecting liver along with the plated cells. Through 28 plated generations over 4 yr the tumor maintained completely stable, morphological heterogeneity. These findings with a complex tumor indicate strongly that its heterogeneity comes not from repeated cellular mutation late in its development, but from diverse potentiality to give rise to cells of specific and differing character, inherent in its individual cells at the time of its multicellular origin.
Full Text
The Full Text of this article is available as a PDF (1.7 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BOYSE E. A. A method for the production of viable cell suspensions from solid tumors. Transplant Bull. 1960 Jan;7:100–104. doi: 10.1097/00006534-196001000-00035. [DOI] [PubMed] [Google Scholar]
- EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
- EDWARDS G. A., FOGH J. Micromorphologic changes in human amnion cells during trypsinization. Cancer Res. 1959 Jul;19(6 Pt 1):608–611. [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]
- Jones F. S., Rous P. ON THE CAUSE OF THE LOCALIZATION OF SECONDARY TUMORS AT POINTS OF INJURY. J Exp Med. 1914 Oct 1;20(4):404–412. doi: 10.1084/jem.20.4.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEVAN A., BIESELE J. J. Role of chromosomes in cancerogenesis, as studied in serial tissue culture of mammalian cells. Ann N Y Acad Sci. 1958 Sep 30;71(6):1022–1053. doi: 10.1111/j.1749-6632.1958.tb46820.x. [DOI] [PubMed] [Google Scholar]
- MADDEN R. E., BURK D. Production of viable single cell suspensions from solid tumors. J Natl Cancer Inst. 1961 Oct;27:841–861. [PubMed] [Google Scholar]
- McLIMANS W. F., DAVIS E. V., GLOVER F. L., RAKE G. W. The submerged culture of mammalian cells; the spinner culture. J Immunol. 1957 Nov;79(5):428–433. [PubMed] [Google Scholar]
- Puck T. T., Marcus P. I. A RAPID METHOD FOR VIABLE CELL TITRATION AND CLONE PRODUCTION WITH HELA CELLS IN TISSUE CULTURE: THE USE OF X-IRRADIATED CELLS TO SUPPLY CONDITIONING FACTORS. Proc Natl Acad Sci U S A. 1955 Jul 15;41(7):432–437. doi: 10.1073/pnas.41.7.432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rous P., Jones F. S. A METHOD FOR OBTAINING SUSPENSIONS OF LIVING CELLS FROM THE FIXED TISSUES, AND FOR THE PLATING OUT OF INDIVIDUAL CELLS. J Exp Med. 1916 Apr 1;23(4):549–555. doi: 10.1084/jem.23.4.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SANFORD K. K., EARLE W. R., LIKELY G. D. The growth in vitro of single isolated tissue cells. J Natl Cancer Inst. 1948 Dec;9(3):229–246. [PubMed] [Google Scholar]
- SEAL S. H. A SIEVE FOR THE ISOLATION OF CANCER CELLS AND OTHER LARGE CELLS FROM THE BLOOD. Cancer. 1964 May;17:637–642. doi: 10.1002/1097-0142(196405)17:5<637::aid-cncr2820170512>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
- SELYE H. Use of granuloma pouch technic in the study of antiphlogistic corticoids. Proc Soc Exp Biol Med. 1953 Feb;82(2):328–333. doi: 10.3181/00379727-82-20108. [DOI] [PubMed] [Google Scholar]