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

Oncogene. 2013 Feb 14;32(7):849-60. doi: 10.1038/onc.2012.112. Epub 2012 Apr 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse