In human breast carcinomas, overexpression of the macrophage colony–stimulating factor (CSF-1) and its receptor (CSF-1R) correlates with poor prognosis. To establish if there is a causal relationship between CSF-1 and breast cancer progression, we crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1op) and followed tumor progression in wild-type and null mutant mice. The absence of CSF-1 affects neither the incidence nor the growth of the primary tumors but delayed their development to invasive, metastatic carcinomas. Transgenic expression of CSF-1 in the mammary epithelium of both Csf1op/Csf1op and wild-type tumor-prone mice led to an acceleration to the late stages of carcinoma and to a significant increase in pulmonary metastasis. This was associated with an enhanced infiltration of macrophages into the primary tumor. These studies demonstrate that the growth of mammary tumors and the development to malignancy are separate processes and that CSF-1 selectively promotes the latter process. CSF-1 may promote metastatic potential by regulating the infiltration and function of tumor-associated macrophages as, at the tumor site, CSF-1R expression was restricted to macrophages. Our data suggest that agents directed at CSF-1/CSF-1R activity could have important therapeutic effects.
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19 March 2001
Article|
March 19 2001
Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy
Elaine Y. Lin,
Elaine Y. Lin
aDepartment of Developmental and Molecular Biology and the Department of Obstetrics/Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health,
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Andrew V. Nguyen,
Andrew V. Nguyen
aDepartment of Developmental and Molecular Biology and the Department of Obstetrics/Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health,
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Robert G. Russell,
Robert G. Russell
bDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461
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Jeffrey W. Pollard
Jeffrey W. Pollard
aDepartment of Developmental and Molecular Biology and the Department of Obstetrics/Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health,
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Elaine Y. Lin
aDepartment of Developmental and Molecular Biology and the Department of Obstetrics/Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health,
Andrew V. Nguyen
aDepartment of Developmental and Molecular Biology and the Department of Obstetrics/Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health,
Robert G. Russell
bDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461
Jeffrey W. Pollard
aDepartment of Developmental and Molecular Biology and the Department of Obstetrics/Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health,
Abbreviations used in this paper: BrdU, 5-bromo-2-deoxy-uridine; DIG, digoxigenin; MMTV, mouse mammary tumor virus; PyMT, polyoma middle T antigen; RT, reverse transcription; Ta, tetracycline activator; Tg, transgene.
Received:
October 23 2000
Revision Requested:
January 08 2001
Accepted:
January 11 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 193 (6): 727–740.
Article history
Received:
October 23 2000
Revision Requested:
January 08 2001
Accepted:
January 11 2001
Citation
Elaine Y. Lin, Andrew V. Nguyen, Robert G. Russell, Jeffrey W. Pollard; Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy. J Exp Med 19 March 2001; 193 (6): 727–740. doi: https://doi.org/10.1084/jem.193.6.727
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