Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy

By Elaine Lin, Andrew V Nguyen, R. Russell, J. Pollard. Journal of Experimental Medicine, 2001

1,690 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/5f83b054e8ef27efe7310b5a7de6da5445d2c34f

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In Immunology

1. A. Mantovani
2. J. Pollard
3. J. Joyce
4. Lisa M. Coussens
5. A. Sica
6. P. Allavena
7. F. Balkwill
8. D. Hanahan

Citations in the corpus

• Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy (2008, positive): “, 2006) or genetically restricted the numbers of monocytes/macrophages (Lin et al., 2001; Lin et al., 2006).”
• Alternative activation of macrophages (2003, background): “Tumour-associated macrophages seem to be incapable of killing established tumours, and they might indeed be trophic for nascent tumour clone”
• Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. (2005, background): “TAMs correlate with poor prognosis in human breast cancer (8, 9), and mouse mammary tumor metastasis is attenuated in animals with reduced numbers of macrophages (10).”
• Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. (2007, methodology): “progression compared with wild-type PyMT mice (12).”
• A Paracrine Loop between Tumor Cells and Macrophages Is Required for Tumor Cell Migration in Mammary Tumors (2004, background): “They also suggest a model to explain the requirement for CSF-1 in invasion and progression to metastasis seen in studies with CSF-1–deficient mice (5).”
• Tumor-associated macrophages: from mechanisms to therapy (2014, background): “…example, CCL2 acting via its receptor CCR2 is a direct mediator of monocyte recruitment to the primary tumor and to metastases in the PYMT model (Cortez-Retamozo et al., 2012; Franklin et al., 2014; Qian et al., 2011) even though this recruitment requires CSF1 (Lin et al., 2001; Qian et al., 2011).”
• CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages (2015, background): “Importantly, ablation of macrophages in the PyMT mice through a null mutation of colony-stimulating factor 1 gene (Csf1op/op) dramatically suppressed lung metastases (Lin et al., 2001), which indicates pivotal roles of macrophages in breast cancer pulmonary metastasis.”
• Role of tumor-associated macrophages in tumor progression and invasion (2006, background): “In turn, genetic studies in mice have shown decreased rates of metastasis to be associated with decreased TAM number [64, 72].”
• Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment (2014, background): “cytokines such as colony-stimulating factor-1 (CSF-1) and endothelial monocyte-activating polypeptide II (EMAPII) have been implicated in the recruitment of monocytes into tumors [28,29].”
• Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. (2004, background): “10 expression produced a significant increase in TAM levels in mammary tumors, leading to accelerated tumor progression and metastasis.(64) Another cytokine implicated in monocyte recruitment is the heparin-binding glycoprotein vascular endothelial growth factor (VEGF).”