Host resistance to metastasis from mouse mammary carcinomas

Abstract

Although undisturbed primary mouse mammary tumors may give rise to overt metastases, these have generally been observed near the terminal stage of progressive tumor growth. Unlike malignant breast disease in women, metastases are seldom the cause of death in mice, and in some strains as few as 2% of mammary tumor hosts may be affected (1). Highly metastatic tumors may, of course, be found, and hosts of the mammary carcinoma WHT all develop metastases (2). Evidence from animal models suggests that host defense reactions against immunogenic tumors may affect the incidence of metastatic spread (3-5). But nonimmunogenic and weakly immunogenic tumors probably represent the majority of mammary carcinomas (2, 6, 7), and this class was once considered outside control by the host. However, natural protective factors are also known which may prevent metastasis independently of specific antitumor immunity (8-10). There are therefore most likely several different biological factors and mechanisms which prevent circulating, viable cancer cells from developing into metastases. But one can not yet generalize whether natural resistance factors or induced resistance factors are the most important, or whether any resistance factors are as important in preventing metastases as is the basic unacceptability of cells in heterotopic locations. This review will not attempt to present a comprehensive analysis of cell-mediated and humoral immunity to mouse mammary tumors because this topic has recently been exhaustively treated in the reviews by Stutman (11) and Blair (12). We will focus primarily on information from in vivo investigations of the role of host resistance in the control of mammary tumor cells progressing through successive levels of metastasis from the primary tumor, through lymphatic or hematogenous dissemination, to colonization of distant organs.

The mutationally activated Met receptor mediates motility and metastasis

“…Second, the tumors from both founders strongly express the mutant Met transgene. Third, mammary carcinoma is the predominant form of malignancy found in female transgenic mice expressing the Tpr-Met oncogene (13), or HGF͞SF (12) neither of those reports mentions the presence of metastasis, the metastatic spread of murine mammary carcinoma has been observed previously (31,32). Although the incidence of metastasis from murine mammary carcinoma often is quite low, systems have been described in which mammary tumors are metastatic (31,32).…”

A survey of in vivo growth characteristics and spontaneous metastasizing potentials of C3H mouse mammary tumors

“…The absence of any histologic evidence of active penetration of pulmonary vessel walls by mammary carcinoma cells (Figs. 4 and 5) excludes invasiveness as a determining factor in the metastasizing potentials of mouse mammary carcinomas, as previously reported (Vaage and Harlos, 1987). Other investigators have also observed that active invasiveness by carcinomatous cells may not be essential in the metastatic process (Dingemans and Mooi, 1986;Fisher and Fisher, 1967;Wallace et al, 1978).…”

“…The expected occurrence of spontaneous pulmonary metastases in 2 out of 3 breeding female C3H/He mice with large spontaneous primary mammary carcinomas (Vaage and Harlos, 1987) provided the opportunity to study a large number of randomly selected tumors from their point and time of origin.…”

“…The purpose of our investigation was therefore to dletermine the relative immunogenicity and spontaneous metastasizing potential of mouse mammary carcinomas under experimental growth conditions as close to natural growth conditions as possible. The expected occurrence of spontaneous pulmonary metastases in 2 out of 3 breeding female C3H/He mice with large spontaneous primary mammary carcinomas (Vaage and Harlos, 1987) provided the opportunity to study a large number of randomly selected tumors from their point and time of origin.…”