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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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GRP94 (gp96) and GRP94 N-Terminal Geldanamycin Binding Domain Elicit Tissue Nonrestricted Tumor Suppression
J. Exp. Med., December 2, 2002; 196(11): 1447 - 1459.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
S. Ostrand-Rosenberg, V. K. Clements, M. Terabe, J. M. Park, J. A. Berzofsky, and S. K. Dissanayake
Resistance to Metastatic Disease in STAT6-Deficient Mice Requires Hemopoietic and Nonhemopoietic Cells and Is IFN-{gamma} Dependent
J. Immunol., November 15, 2002; 169(10): 5796 - 5804.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
C. W. Wong, C. Song, M. M. Grimes, W. Fu, M. W. Dewhirst, R. J. Muschel, and A.-B. Al-Mehdi
Intravascular Location of Breast Cancer Cells after Spontaneous Metastasis to the Lung
Am. J. Pathol., September 1, 2002; 161(3): 749 - 753.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
B. A. Pulaski, M. J. Smyth, and S. Ostrand-Rosenberg
Interferon-{gamma}-dependent Phagocytic Cells Are a Critical Component of Innate Immunity against Metastatic Mammary Carcinoma
Cancer Res., August 1, 2002; 62(15): 4406 - 4412.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. P. V. Shekhar, A. Lyakhovich, D. W. Visscher, H. Heng, and N. Kondrat
Rad6 Overexpression Induces Multinucleation, Centrosome Amplification, Abnormal Mitosis, Aneuploidy, and Transformation
Cancer Res., April 1, 2002; 62(7): 2115 - 2124.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
E. Cretney, K. Takeda, H. Yagita, M. Glaccum, J. J. Peschon, and M. J. Smyth
Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice
J. Immunol., February 1, 2002; 168(3): 1356 - 1361.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
P. Parajuli, V. Pisarev, J. Sublet, A. Steffel, M. Varney, R. Singh, D. LaFace, and J. E. Talmadge
Immunization with Wild-Type p53 Gene Sequences Coadministered with Flt3 Ligand Induces an Antigen-specific Type 1 T-Cell Response
Cancer Res., November 1, 2001; 61(22): 8227 - 8234.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C.-Y. Li, J. B. Little, K. Hu, W. Zhang, L. Zhang, M. W. Dewhirst, and Q. Huang
Persistent Genetic Instability in Cancer Cells Induced by Non-DNA-damaging Stress Exposures
Cancer Res., January 1, 2001; 61(2): 428 - 432.
[Abstract] [Full Text]

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 J. Immunol.Home page
S. Ostrand-Rosenberg, M. J. Grusby, and V. K. Clements
Cutting Edge: STAT6-Deficient Mice Have Enhanced Tumor Immunity to Primary and Metastatic Mammary Carcinoma
J. Immunol., December 1, 2000; 165(11): 6015 - 6019.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
Q. Huang, J. K. Hu, F. Lohr, L. Zhang, R. Braun, J. Lanzen, J. B. Little, M. W. Dewhirst, and C.-Y. Li
Heat-induced Gene Expression as a Novel Targeted Cancer Gene Therapy Strategy
Cancer Res., July 1, 2000; 60(13): 3435 - 3439.
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 Cancer Res.Home page
B. A. Pulaski, D. S. Terman, S. Khan, E. Muller, and S. Ostrand-Rosenberg
Cooperativity of Staphylococcal aureus Enterotoxin B Superantigen, Major Histocompatibility Complex Class II, and CD80 for Immunotherapy of Advanced Spontaneous Metastases in a Clinically Relevant Postoperative Mouse Breast Cancer Model
Cancer Res., May 1, 2000; 60(10): 2710 - 2715.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
V. Pethe and P. V. M. Shekhar
Estrogen Inducibility of c-Ha-ras Transcription in Breast Cancer Cells. IDENTIFICATION OF FUNCTIONAL ESTROGEN-RESPONSIVE TRANSCRIPTIONAL REGULATORY ELEMENTS IN EXON 1/INTRON 1 OF THE c-Ha-ras GENE
J. Biol. Chem., October 22, 1999; 274(43): 30969 - 30978.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
A. Bandyopadhyay, Y. Zhu, M. L. Cibull, L. Bao, C. Chen, and L. Sun
A Soluble Transforming Growth Factor {beta} Type III Receptor Suppresses Tumorigenicity and Metastasis of Human Breast Cancer MDA-MB-231 Cells
Cancer Res., October 1, 1999; 59(19): 5041 - 5046.
[Abstract] [Full Text] [PDF]


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