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CEACAM-1 negatively regulates G-CSF production by breast tumor associated macrophages that mediate tumor angiogenesis.
MedLine Citation:
PMID:  23319418     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
CEACAM1, a cell adhesion molecule expressed on epithelial cells and activated immune cells, is down-regulated in many cancers and plays a role in inhibition of inflammation in part by inhibition of G-CSF production by myeloid cells. Since macrophages are associated with a poor prognosis in breast cancer, but play important roles in normal breast, we hypothesized that CEACAM1 down-regulation would lead to tumor promotion under inflammatory conditions. Co-cultures of pro-inflammatory M1 macrophages with CEACAM1 negative MCF7 breast cells produced high levels of G-CSF (10 ng/mL) compared to CEACAM1 transfected MCF7/4S cells (1 ng/mL) or anti-inflammatory M2 macrophage co-cultures (0.5 or 0.1 ng/mL, MCF7 or MCF7/4S, respectively). The expression of CEACAM1 on M1s was much greater than for M2s and was only observed in co-cultures with either MCF7 or MCF7/4S cells. When M1 macrophages were mixed with MCF7 cells and implanted in murine mammary fat pads of NOD/SCID mice, tumor size and blood vessel density were significantly greater than MCF7 or MCF7/4S only tumors which were hardly detected after 8 weeks of growth. In contrast, M1 cells had a much reduced effect on MCF7/4S tumor growth and blood vessel density, indicating that the tumor inhibitory effect of CEACAM1 is most likely related to its anti-inflammatory action on inflammatory macrophages. These results support our previous finding that CEACAM1 inhibits both G-CSF production by myeloid cells and G-CSF stimulated tumor angiogenesis. © 2013 Wiley Periodicals, Inc.
Authors:
Sridhar Samieni; Zhifang Zhang; John E Shively
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 UICC.
Affiliation:
City of Hope Irell&Manella Graduate School of Biological Sciences, Duarte, CA 91010; Department of Immunology, Beckman Research Institute of City of Hope, 1450 E. Duarte Rd, Duarte CA 91010, USA.
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