Carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 as biomarkers in pancreatic cancer

PLoS One. 2014 Nov 19;9(11):e113023. doi: 10.1371/journal.pone.0113023. eCollection 2014.

Abstract

Background: Aim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 in pancreatic adenocarcinoma (PDAC).

Experimental design: CEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC) and by enzyme linked immunosorbent assays.

Results: Presence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC) and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS). The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group.

Conclusion: The effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Survival Analysis

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CD66 antigens
  • CEACAM5 protein, human
  • CEACAM6 protein, human
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • GPI-Linked Proteins

Grant support

The authors have no support or funding to report.