Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy

Elaine Lin, A. V. Nguyen, R. G. Russell, J. W. Pollard

Research output: Contribution to journalArticle

1096 Citations (Scopus)

Abstract

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 (Csf op) 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 Csf1 op/Csf1 op 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.

Original languageEnglish (US)
Pages (from-to)727-739
Number of pages13
JournalJournal of Experimental Medicine
Volume193
Issue number6
DOIs
StatePublished - Mar 19 2001
Externally publishedYes

Fingerprint

Macrophage Colony-Stimulating Factor
Breast Neoplasms
Macrophage Colony-Stimulating Factor Receptors
Neoplasms
Macrophages
Carcinoma
Therapeutic Uses
Growth
Transgenic Mice
Breast
Epithelium
Neoplasm Metastasis
Lung
Mutation
Incidence

Keywords

  • Breast cancer
  • Macrophages
  • Metastasis
  • Mouse
  • Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. / Lin, Elaine; Nguyen, A. V.; Russell, R. G.; Pollard, J. W.

In: Journal of Experimental Medicine, Vol. 193, No. 6, 19.03.2001, p. 727-739.

Research output: Contribution to journalArticle

Lin, Elaine ; Nguyen, A. V. ; Russell, R. G. ; Pollard, J. W. / Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. In: Journal of Experimental Medicine. 2001 ; Vol. 193, No. 6. pp. 727-739.
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