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A murine model of spontaneous metastasis of mammary adenocarcinomas in mice was developed by serial transplantation of spontaneous BALB/cfC3H/ Crgl tumours into the mammary gland. Through 8 transplant generations, 5 lines demonstrated maintenance of metastatic phenotype and consistent gross and histological morphology and growth properties. Tumour lines M12, M35 , and M51 metastasized from the mammary gland with overall frequencies of 53, 80, and 85%, respectively. Line T5 was weakly metastatic, capable of a minor degree of lung colonization in 8% of hosts, while line WT2 failed to establish any grossly or histologically detectable pulmonary foci. The significance of the mammary gland as transplant site was shown by comparing the growth and metastasis of these lines in mammary gland with that observed upon subcutaneous transplantation. Subcutaneous metastatic frequency of one tumour line was significantly reduced from that obtained when grown in the mammary gland while histological organization differed markedly in 2 of the tumours. Furthermore, while tumours implanted into the gland grew as well encapsulated masses, the same tumours grown subcutaneously frequently invaded the body wall and occasionally colonized adjacent peritoneal organs and, more often, mesenteries. Intravenous injection of dissociated tumours further emphasized the importance of events that occur at the primary site. There was no correlation between spontaneous metastatic ability and the capacity to colonize the lung following i.v. inoculation. This study demonstrates the importance of transplant site in the assessment of metastasis in experimental systems.

Metastasis of murine mammary tumour lines from the mammary gland and ectopic sites