Abstract
Our previous studies using randomly integrated plasmid DNA as unique clonotypic markers of SP1 mouse mammary tumor cells transplanted into syngeneic CBA/J or nude mice demonstrated reproducible selection and eventual overgrowth of the primary transplant tumors by genotypically distinct metastatic subclones. Two independent metastatic SP1 clones, __neo__5 and __ras__1, were shown to exhibit „clonal dominance”︁ relative to the non‐metastatic SP1 tumor‐cell population. These results suggested that the capacity for preferential growth within the tumors may be related to cellular properties associated with metastatic ability. To investigate the clonal interactions of metastatic SPI clones present within the same tumor mass, we have analyzed tumors composed of paired mixtures of __neo__5 and __ras__1. The tumors were monitored for the relative proportion of each clone by Southern blot analysis. The __ras__1 clone was found to dominate over the __neo__5 clone in the majority of tumors examined, even when present as 1% of the mixed inoculum. This represents a 20‐ to 50‐fold enrichment of __ras__1, while the proportion of __neo__5 within the tumors was reduced at least 5‐fold. No evidence for selection of either clone was seen during co‐culture __in vitro. Neo__5 and __ras__1 are indistinguishable with respect to tumor igenic and metastatic potential when inoculated separately into different mice, suggesting that clonal dominance is independent of metastatic ability. Analysis of the metastases resulting from mixed inocula indicates that it is possible for a subpopulation representing less than 1% of the primary tumor mass to give rise to metastases. This also suggests that the process of metastasis within metastatic tumors is independent of clonal dominance.