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

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.

• Authors: A Arabzadeh, C Chan, A-L Nouvion, V Breton, S Benlolo, L DeMarte, C Turbide, P Brodt, L Ferri, N Beauchemin
• Journal: Oncogene (Oncogene) Vol. 32 Issue 7 Pg. 849-60 (Feb 14 2013) ISSN: 1476-5594 [Electronic] England
• PMID: 22469976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinoembryonic Antigen
• Ceacam1 protein, mouse

Topics

• Animals
• Carcinoembryonic Antigen (genetics, metabolism, physiology)
• Carcinoma (blood supply, genetics, pathology)
• Cell Proliferation
• Cell Survival
• Colorectal Neoplasms (blood supply, genetics, pathology)
• Liver (metabolism, pathology)
• Mice
• Mice, Knockout
• Models, Biological
• Neoplasm Metastasis
• Neovascularization, Pathologic (genetics)
• Organ Specificity (genetics)
• Tumor Cells, Cultured