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[Cancer Research 52, 1399-1405, March 15, 1992]
© 1992 American Association for Cancer Research
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Selective Events in the Metastatic Process Defined by Analysis of the Sequential Dissemination of Subpopulations of a Mouse Mammary Tumor1

Cheryl J. Aslakson and Fred R. Miller2

Breast Cancer Biology Program, Michigan Cancer Foundation [C. J. A., F. R. M.], and Department of Immunology and Microbiology, Wayne State University School of Medicine [C. J. A.], Detroit, Michigan 48201

To identify selective steps in metastasis, those that eliminate nonmetastatic tumor cells more efficiently than metastatic cells, we have evaluated the sequential dissemination of tumor cells from a mammary fatpad, using both metastatic (4T1 and 66cl4) and nonmetastatic (67NR, 168FARN, and 4TO7) subpopulations of a single mouse mammary tumor. Each of these variant subpopulations is resistant to one or more selective drugs so they could be quantitatively identified by colony formation in selective media. We found that the 2 metastatic cell lines metastasized by different routes and that the nonmetastatic tumor cell lines failed at different points in dissemination. Line 67NR did not leave the primary site; clonogenic tumor cells were not detected in the nodes, blood, or lungs during the experiment (7 weeks). Tumor line 168FARN disseminated from the primary tumor because clonogenic cells were cultured from the draining lymph nodes throughout the experiment. However, dissemination essentially stopped in the node as cells were rarely isolated from blood, lungs, or livers. Whether 168FARN cells failed to reach these tissues or were killed very rapidly after traversing the lymph node is unknown. Line 4TO7 cells disseminated via the blood and were consistently recovered from lungs by day 19 but failed to proliferate. This panel of 5 subpopulations thus identifies different points of selective failure in tumor cell dissemination and should be valuable in the assessment of antimetastatic therapies.

1 Supported by USPHS Grant CA28366 from the National Cancer Institute and a grant from the Concern Foundation.

2 To whom requests for reprints should be addressed, at: Michigan Cancer Foundation, 110 East Warren Avenue, Detroit, MI 48201.

Received 8/ 8/91. Accepted 12/30/91.




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