Cellular Basis for Regulation of Tumor Growth
The association of host-derived cells with progressing transplantable tumors raises several important issues. For example, the relevance of the host cells to tumor growth is not clear, and the mechanisms that determine whether macrophages, lymphocytes, or granulocytes infiltrate the tumor mass are not understood. Similarly, it is not clear whether tumor-associated host cells (TAHC) play a role in therapy-induced regression, and to what extent manipulation of TAHC is possible either within the tumor or before they reach the tumor (see review by Evans, 1977c). Other questions arise from these, such as whether any influence that TAHC may appear to exert on tumor growth (induced regression or stimulation) is mediated directly, by soluble mediators or by acting in cooperation with other cell types. Moreover, while an effect may appear to occur locally, that is, progression or regression may be associated with the presence of particular cell types, the effect may actually be mediated from a distance, for example, by soluble mediators that originate at a distant site and circulate through the tumor and react directly with the neoplastic cells or with tumor-associated host effector cells. Dissection of the wide array of reactions that probably occur is obviously difficult and complex, but as a starting point it is a reasonable assumption that some of the answers may lie at the site of tumor growth, not necessarily to the exclusion of reactions occurring peripherally but perhaps in concert with them. This is not a comprehensive review and will cover only certain aspects of the cellular basis for regulation of tumor growth, having special reference to events occurring at the level of the tumor mass. Some experiments on the accumulation of host cells will be described, together with a discussion on the implications of such accumulation. The review will explore the possibility that tumor progression might be associated with cells able to enhance neoplastic cell proliferation directly, or indirectly by preventing cells generally associated with graft rejection from expressing cytotoxicity. Finally, the effects of drugs on the cellular composition of tumors during regression and regrowth following a period of remission will be discussed.
KeywordsNeoplastic Cell Cellular Basis Irradiate Mouse Tumor Cell Implantation Whole Body Irradiation
Unable to display preview. Download preview PDF.
- Eccles, S. A., Bandlow, G., and Alexander, P., 1976, Monocytosis associated with growth of transplanted syngeneic sarcomas differing in immunogenicity, Br. J. Cancer 34:20.Google Scholar
- Evans, R., 1972, Macrophages in syngeneic animal tumors, Transplantation 14: 468.Google Scholar
- Evans, R., 1973, Macrophages and the tumor-bearing host, Br. J. Cancer 22 (i): 19.Google Scholar
- Evans, R., 1976, Tumor macrophages in host immunity to maligancies, in: The Macrophage in Neoplasia ( M. A. Fink, ed.), p. 27, Academic Press, New York.Google Scholar
- Evans, R., 1977c, Macrophages in solid tumors, in: The Macrophage and Cancer ( K. James, B. McBride, and A. Stuart, eds.), p. 321, Econoprint, Edinburgh.Google Scholar
- Evans, R., and Alexander, P., 1976, Mechanisms of extracellular killing of nucleated mammalian cells by macrophages, in: Immunobiology of the Macrophage ( D. S. Nelson, ed.), p. 536, Academic Press, New York.Google Scholar
- Hibbard, A. D., and Metcalf, D., 1971, Proliferation of macrophage and granulocyte precursors in response to primary and transplanted tumors, Isr. J. Med. Sci. 7: 202.Google Scholar
- Moore, M., and Williams, D. E., 1973, Contribution of host immunity to cyclophosphamide therapy of a chemically-induced murine fibrosarcoma, Int. J. Cancer 11:358.Google Scholar
- Normann, S. J., Schardt, M., and Sorkin, E., 1977, Do tumors escape suveillance by depression of macrophage inflammation? in: The Macrophage and Cancer ( K. James, B. McBride, and A. Stuart, eds.), p. 247, Econoprint, Edinburgh.Google Scholar
- Russell, S. W., Doe, W. F., and McIntosh, A. T., 1977a, A non-cytolytic stage of macrophage activation in Maloney sarcomas, in: The Macrophage and Cancer ( K. James, B. McBride, and A. Stuart, eds.), p. 341, Econoprint, Edinburgh.Google Scholar
- Snyderman, R., and Pike, M. C., 1976, Defective macrophage migration produced by neo-plasms: Identification of an inhibitor of macrophage chemotaxis, in: The Macrophage in Neoplasia ( M. A. Fink, ed.), p. 49, Academic Press, New York.Google Scholar