Document Detail

Carcinoembryonic antigen-related cell adhesion molecule 1 negatively regulates granulocyte colony-stimulating factor production by breast tumor-associated macrophages that mediate tumor angiogenesis.
MedLine Citation:
PMID:  23319418     Owner:  NLM     Status:  MEDLINE    
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a cell adhesion molecule expressed on epithelial cells and activated immune cells, is downregulated in many cancers and plays a role in inhibition of inflammation in part by inhibition of granulocyte colony-stimulating factor (G-CSF) production by myeloid cells. As macrophages are associated with a poor prognosis in breast cancer, but play important roles in normal breast, we hypothesized that CEACAM1 downregulation would lead to tumor promotion under inflammatory conditions. Cocultures of proinflammatory 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 cocultures (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 observed only in cocultures with either MCF7 or MCF7/4S cells. When M1 macrophages were mixed with MCF7 cells and implanted in murine mammary fat pads of nonobese diabetic/severe combined immunodeficient 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.
Sridhar Samineni; Zhifang Zhang; John E Shively
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-12
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-05-15     Completed Date:  2013-07-11     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  394-407     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Anti-Inflammatory Agents / pharmacology
Antigens, CD / metabolism*
Breast Neoplasms / pathology*
Carcinoembryonic Antigen / metabolism
Cell Adhesion Molecules / metabolism*
Cell Differentiation
Coculture Techniques
Collagen / chemistry
Cytokines / metabolism
Drug Combinations
Gene Expression Regulation, Neoplastic
Granulocyte Colony-Stimulating Factor / metabolism*
Laminin / chemistry
MCF-7 Cells
Macrophages / metabolism*
Mice, SCID
Monocytes / cytology
Neoplasm Transplantation
Neovascularization, Pathologic*
Proteoglycans / chemistry
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Antigens, CD; 0/CD66 antigens; 0/Carcinoembryonic Antigen; 0/Cell Adhesion Molecules; 0/Cytokines; 0/Drug Combinations; 0/Laminin; 0/Proteoglycans; 119978-18-6/matrigel; 143011-72-7/Granulocyte Colony-Stimulating Factor; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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