Characteristics of Metastasizing and Non-Metastasizing Tumors and Their Interaction with the Host Immune System in the Development of Metastasis

Abstract

Most animal solid tumors grow expansively at the site of origin without invading the surrounding soft tissue stroma or metastasizing to distant organs, even when they become very large. On the other hand, the single most critical attribute of human cancers is their capacity to invade and metastasize to vital secondary organs resulting in death of the patient. However, the lack of invasion and metastasis in laboratory animal tumors is not because the tumor cells do not enter into the systemic circulation of the host, for a large number of viable tumor cells are readily harvested from the venous as well as the arterial blood of animals bearing a localized tumor (Kim, 1966; Butler and Gullino, 1975), and yet such cells seem incapable of establishing secondary colonies. Thus, there seems to be fundamental difference in the biological property between human and animal tumor cells, and At may lie in the manner by which these tumors are developed. Laboratory investigators in general tend to favor fast growing tumors with a short latent period irrespective of the type of oncogenic agents used. Such tumors are frequently highly immunogenic (Prehn, 1975), due probably to insufficient time for the developing tumor cells to undergo immunological and other host-generated selective processes. Human cancers, on the other hand, particularly carcinomas are usually a late event in our life, and also most of them are non-immunogenic. Such characteristics are likely to have been brought about by more subtle oncogenic exposures and by repeated selective pressures produced by host immune surveillance mechanism during the life of patients. These suppositions were experimentally tested in young adult female rats by exposing them to chemical carcinogen together with the application of non-specific and specific immuno-suppression and stimulation to bring out weakly or non-immunogenic tumor cells slowly over an extended period of time. Such laboratory manipulation yielded many spontaneously metastasizing rat mammary carcinomas with many of their characteristics similar to those of breast cancer in women (Kim, 1970, 1977). Table 1 lists 9 representatives of such tumors that have been established and are maintained in the highly inbred strain of W/Fu rats in our laboratory to carry out various studies outlined in this paper. In order to learn the nature of metastatic potential of tumor cells, their biological, biochemical and immunological properties were compared with those of conventional, non-metastasizing, chemically-induced, syngeneic rat tumors that had been matched according to the degree of glandular differentiation and growth rate in normal syngeneic rats.