Summary
EMT6 mammary sarcoma cells were grown in vitro as multicellular spheroids to model for the heterogeneity of microenvironments and structural changes which develop in many tumors, including micrometastases. Spheroids of 700–900 gm diameter were implanted into and recovered at different times from the peritoneal cavities of sensitized or nonsensitized allogeneic and syngeneic mice. The colony forming efficiency of spheroid tumor cells recovered at 24 and 48 h from sensitized allogeneic mice was markedly decreased as compared with those from nonsensitized allogeneic or syngeneic animals. These recovered spheroids were extensively infiltrated by both lymphocytes and macrophages, which ultrastructurally had very close membrane associations with tumor cells. Host cells recovered from spheroids exhibited cy to toxic activity in an in vitro51Cr release assay. Thus, multicellular spheroids in vivo provide a unique experimental model to study the functional capacity of host cells within a spheroical tumor. Although lacking the stroma and the vasculature of in vivo solid tumors, this model does have many similarities to in vivo tumors and is thus suitable for studying the tumor cell-host cell interactions within the tumor microenvironment. In addition, the system offers the potential for quantitative study of the effects of treatment modalities on tumor cell-host cell interactions.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Baserga, R.: The Cell Cycle and Cancer. New York: Dekker 1971
Cerottini, J.C., Brunner, K.T.: Cell-mediated cytotoxicity, allograft rejection and tumor immunity. Adv. Immunol.18, 67–132 (1974)
Fowler, J.F.: Current aspects of radiobiology as applied to radiotherapy. Clin. Radiol.23, 257–262 (1972)
Gillespie, G.Y., Hansen, C.B., Haskins, R.G., Russell, S.W.: Inflammatory cells in solid murine neoplasms. IV. Cytolytic T lymphocytes isolated from regressing and progressing Maloney sarcomas. J. Immunol.119, 564–570 (1977)
Haskill, J.S., Proctor, J.W., Yamomura, Y.: Host responses within solid tumors. I. Monocytic effector cells within rat sarcomas. J. Natl. Cancer Inst.54, 387–393 (1975)
Herberman, R.B.: Cell-mediated immunity to tumor cells. Adv. Cancer Res.19, 207–249 (1974)
Kaplan, H.S.: On the relative importance of hypoxic cells for the radiotherapy of human tumors. Eur. J. Cancer10, 275–280 (1974)
MacDonald, H.R., Howell, R.L.: The multicellular spheroid as a model tumor allograft. I. Quantitative assessment of spheroid destruction in alloimmune mice. Transplant.25, 136–140 (1978)
MacDonald, J.R., Howell, R.L., Mc McFarlane, D.L.: The multicellular spheroid as a model tumor allograft. II. Characterization of the spheroid infiltrating cytotoxic cells. Transplant.25, 141–145 (1978)
Penney, D.P., Rubin, P.: Specific early fine structural changes in the lung following radiation. Int. J. Radiation Oncol. Biol. Phys.2, 1123–1132 (1977)
Pross, H.F., Kerbel, R.S.: An assessment of intratumor phagocytic and surface marker-bearing cells in a series of autochthomous and early passaged chemically induced murine sarcomas. J. Natl. Cancer Inst.57, 1157–1167 (1976)
Roberts, Hayry, P.: Effector mechanisms in an allograft rejection. I. Assembly of “sponge matrix” allografts. Cell Immunol.26, 160–167 (1976)
Roberts, P.J., Hayry, P.: Effector mechanisms in allograft rejection. II. Density, electrophoresis, and size fractionation of allograft-infiltrating cells demonstrating several classes of killer cells. Cell Immunol.30, 236–253 (1977)
Rockwell, S.: In vivo-in vitro tumor systems: New models for studying the response of tumors to therapy. Lab. Animal Sci.27, 831–851 (1977)
Rockwell, S.C., Kallman, R.F., Fajardo, L.F.: Characteristics of a serially socially transplanted mouse mammary tumor and its tissue culture adapted derivative. J. Natl. Cancer Inst.49, 735–747 (1972)
Russell, S.W., Doe, W.F., Haskins, R.G., Cochrane, C.G.: Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent in inflammatory cells. Int. J. Cancer18, 322–330 (1976)
Sanderson, C.J.: The mechanism of T cell mediated cytotoxicity. I. The release of different cell components Proc. R. Soc. Land B.192, 221–240 (1976)
Strom, T.B., Tilney, N.L., Paradysz, J.M., Bancewicz, J., Carpenter, C.B.: Cellular components of allograft rejection: Identity, specificity, and cytolytic functions of cells infiltrating acutely rejecting allografts. J. Immunol.118, 2020–2026 (1977)
Sutherland, R.M., Durand, R.E.: Radiation response of multicell spheroids: An in vitro tumor model. Curr. Top. Radiat. Res.11, 87–139 (1976)
Sutherland, R.M., MacDonald, J.R., Howell, R.L.: Multicellular spheroids: A new model target for in vitro studies of immunity to solid tumor allografts. J. Natl. Cancer Inst.58, 1849–1853 (1977)
Tilney, N.L., Strom, T.B., MacPheison, S.G., Carpenter, C.G.: Studies on infiltrating host cells harvested from acutely rejecting rat cardiac allografts. Surgery79, 209–217 (1976)
Author information
Authors and Affiliations
Additional information
This investigation was supported by grants CA-20329, CA-11051, and by Cancer Center Core Support Grant 2-P30-CA-11198-10. All were awarded by the National Cancer Institute, Department of Health, Education, and Welfare
Rights and permissions
About this article
Cite this article
Lord, E.M., Penney, D.P., Sutherland, R.M. et al. Morphological and functional characteristics of cells infiltrating and destroying tumor multicellular spheroids in vivo. Virchows Archiv B Cell Pathol 31, 103–116 (1979). https://doi.org/10.1007/BF02889928
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02889928