Role of concomitant resistance in the development of murine lung metastases

An attempt was made to explain the distinct lung metastatic patterns of 2 mammary adenocarcinomas with a common BALB/c origin: M 3 , which does not induce spontaneous metastases, and MM 3 with an almost 100% incidence. No difference between the 2 tumors was detected with respect to host mononuclear cell content, degree of immunogenicity or lung‐colony‐forming ability. Conversely, there was a marked difference in the capacity to induce concomitant resistance: M 3 ‐bearing mice induced stronger and earlier resistance against i.v. challenge of both M3 and MM 3 tumor cells than MM 3 ‐bearing mice; this resistance was expressed as lower number of lung metastases and lower tumor‐cell proliferation in metastatic nodules. M 3 was also able to control the development of spontaneous metastases: metastases developed in all M 3 ‐excised mice, compared with none in M 3 ‐bearing mice, while MM 3 ‐bearing mice also bearing a secondary M 3 tumor developed fewer metastases than mice bearing MM 3 only. This anti‐metastatic effect does not appear to depend on classical immunological mechanisms since no difference could be detected between the 2 tumors in response to T cells, NK, macrophages or antibodies.