Host-related carcinoembryonic antigen cell adhesion molecule 1 promotes metastasis of colorectal cancer

A Arabzadeh; C Chan; A-L Nouvion; V Breton; S Benlolo; L DeMarte; C Turbide; P Brodt; L Ferri; N Beauchemin

doi:10.1038/onc.2012.112

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Host-related carcinoembryonic antigen cell adhesion molecule 1 promotes metastasis of colorectal cancer

Journal article

Peer reviewed

Host-related carcinoembryonic antigen cell adhesion molecule 1 promotes metastasis of colorectal cancer

A Arabzadeh, C Chan, A-L Nouvion, V Breton, S Benlolo, L DeMarte, C Turbide, P Brodt, L Ferri and N Beauchemin

Oncogene, Vol.32(7), pp.849-860

02/14/2013

DOI: 10.1038/onc.2012.112

PMID: 22469976

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Abstract

Liver metastasis is the predominant cause of colorectal cancer (CRC)-related mortality in developed countries. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell adhesion molecule with reduced expression in early phases of CRC development and thus functions as a tumor growth inhibitor. However, CEACAM1 is upregulated in metastatic colon cancer, suggesting a bimodal role in CRC progression. To investigate the role of this protein in the host metastatic environment, Ceacam1(-/-) mice were injected intrasplenically with metastatic MC38 mouse CRC cells. A significant reduction in metastatic burden was observed in Ceacam1(-/-) compared with wild-type (WT) livers. Intravital microscopy showed decreased early survival of MC38 cells in Ceacam1(-/-) endothelial environment. Metastatic cell proliferation within the Ceacam1(-/-) livers was also diminished. Bone marrow-derived cell recruitment, attenuation of immune infiltrates and diminished CCL2, CCL3 and CCL5 chemokine production participated in the reduced Ceacam1(-/-) metastatic phenotype. Transplantations of WT bone marrow (BM) into Ceacam1(-/-) mice fully rescued metastatic development, whereas Ceacam1(-/-) BM transfer into WT mice showed reduced metastatic burden. Chimeric immune cell profiling revealed diminished recruitment of CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) to Ceacam1(-/-) metastatic livers and adoptive transfer of MDSCs confirmed the involvement of these immune cells in reduction of liver metastasis. CEACAM1 may represent a novel metastatic CRC target for treatment.

Carcinoembryonic Antigen - physiology

Liver - pathology

Cell Proliferation

Colorectal Neoplasms - blood supply

Cell Survival

Colorectal Neoplasms - genetics

Liver - metabolism

Carcinoembryonic Antigen - genetics

Carcinoembryonic Antigen - metabolism

Mice, Knockout

Organ Specificity - genetics

Neoplasm Metastasis

Animals

Models, Biological

Carcinoma - genetics

Neovascularization, Pathologic - genetics

Carcinoma - blood supply

Mice

Tumor Cells, Cultured

Carcinoma - pathology

Colorectal Neoplasms - pathology

Details

Title: Subtitle: Host-related carcinoembryonic antigen cell adhesion molecule 1 promotes metastasis of colorectal cancer
Creators: A Arabzadeh - Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada
C Chan
A-L Nouvion
V Breton
S Benlolo
L DeMarte
C Turbide
P Brodt
L Ferri
N Beauchemin
Resource Type: Journal article
Publication Details: Oncogene, Vol.32(7), pp.849-860
Publisher: England
DOI: 10.1038/onc.2012.112
PMID: 22469976
ISSN: 0950-9232
eISSN: 1476-5594
Grant note: Canadian Institutes of Health Research
Language: English
Date published: 02/14/2013
Academic Unit: Surgery; Radiation Oncology
Record Identifier: 9984047648102771

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