title: 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.affiliation: Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Arabzadeh
authors.forename: C
authors.initials: C
authors.lastname: Chan
authors.forename: A-L
authors.initials: AL
authors.lastname: Nouvion
authors.forename: V
authors.initials: V
authors.lastname: Breton
authors.forename: S
authors.initials: S
authors.lastname: Benlolo
authors.forename: L
authors.initials: L
authors.lastname: DeMarte
authors.forename: C
authors.initials: C
authors.lastname: Turbide
authors.forename: P
authors.initials: P
authors.lastname: Brodt
authors.forename: L
authors.initials: L
authors.lastname: Ferri
authors.forename: N
authors.initials: N
authors.lastname: Beauchemin
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse