Distinct expression of cytokeratin, N-cadherin and CD133 in circulating tumor cells of metastatic breast cancer patients

Future Oncol. 2014 Aug;10(10):1751-65. doi: 10.2217/fon.14.58.

Abstract

Aim: Circulating tumor cells (CTCs) appear as potential candidates to predict the ability of breast tumors to metastasize. Moreover, epithelial-mesenchymal transition (EMT) and stem cell features are major mechanisms for metastasis.

Patients & methods: Using a triple fluorescence technique, the expression of EMT (N-cadherin) and stem cell markers (CD133) was analyzed in CTCs detected via cytokeratin in blood samples from 26 metastatic breast cancer patients.

Results: We detected CTCs in 100% of the patients (n = 831 CTCs). In total, 67% of the CTCs were N-cadherin and CD133 negative. Nonetheless, 87.8 and 57.6%, respectively, of the CTCs that expressed one marker coexpressed the other. Both double-negative and double-positive CTCs were present in more than 90% of the patients. Within the CTCs of each patient, we demonstrated striking heterogeneities of marker expressions, cell shapes, clusters and sizes.

Conclusion: These data outline the importance of characterizing CTCs, especially through stem cell and EMT markers.

Keywords: CD133; EMT; N-cadherin; breast cancer; circulating tumor cells; stem cells.

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Cohort Studies
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Keratins / genetics
  • Keratins / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Stem Cells
  • Peptides / genetics
  • Peptides / metabolism*
  • Reproducibility of Results

Substances

  • AC133 Antigen
  • Antigens, CD
  • Biomarkers, Tumor
  • Cadherins
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Keratins