Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development Journal Article


Authors: Pyonteck, S. M.; Gadea, B. B.; Wang, H. W.; Gocheva, V.; Hunter, K. E.; Tang, L. H.; Joyce, J. A.
Article Title: Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development
Abstract: Tumor-associated macrophages have recently emerged as a key regulatory cell type during cancer progression, and have been found to promote tumor malignancy in the majority of studies performed to date. We show in this study that CD68 macrophages positively correlate with tumor grade and liver metastasis in human pancreatic neuroendocrine tumors (PNETs). To investigate the potential mechanisms whereby macrophages can promote PNET progression, we crossed the RIP1-Tag2 (RT2) mouse model of pancreatic islet cancer to colony-stimulating factor-1 (CSF-1)-deficient Csf1 op/op mice, which have reduced numbers of tissue macrophages. Csf1 op/op RT2 mice had a substantial reduction in cumulative tumor burden, which interestingly resulted from a significant decrease in angiogenic switching and tumor number, rather than an evident effect on tumor growth. In the tumors that did develop in CSF-1-deficient animals, however, there were no significant differences in tumor cell proliferation, apoptosis, angiogenesis or invasion. CSF-1 deficiency decreased macrophage infiltration by approximately 50% during all stages of RT2 tumor progression. Interestingly, several cytokines were upregulated in CSF-1-deficient RT2 tumors, and neutrophil infiltration was increased. These results show that macrophages are important for promoting PNET development and suggest that additional factors contribute to the recruitment and survival of myeloid cells in RT2 tumors in the absence of CSF-1. © 2012 Macmillan Publishers Limited All rights reserved.
Keywords: tumor microenvironment; tumor-associated macrophage; human pnet; myeloid cell
Journal Title: Oncogene
Volume: 31
Issue: 11
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2012-03-15
Start Page: 1459
End Page: 1467
Language: English
DOI: 10.1038/onc.2011.337
PROVIDER: scopus
PUBMED: 21822305
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 2 April 2012" - "CODEN: ONCNE" - "Source: Scopus"
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MSK Authors
  1. Bedrick B Gadea
    4 Gadea
  2. Laura Hong Tang
    447 Tang
  3. Johanna A Joyce
    67 Joyce
  4. Vasilena Gocheva
    15 Gocheva
  5. Hao-Wei Wang
    8 Wang
  6. Karen Hunter
    6 Hunter
  7. Stephanie Harris
    4 Harris