title: The number of tumorspheres cultured from peripheral blood is a predictor for presence of metastasis in patients with breast cancer.
abstract: BACKGROUND
  Tumor metastases are the major cause of cancer morbidity and mortality. A subpopulation of tumor cells with stem-like properties is assumed to be responsible for tumor invasion, metastasis, heterogeneity and therapeutic resistance. This population is termed cancer stem cells (CSCs). We have developed a simple method for identification and characterization of circulating cancer stem cells among circulating epithelial tumor cells (CETCs).
  
  
  METHODS
  CETCs were cultured under conditions favoring growth of tumorspheres from 72 patients with breast cancer, including a subpopulation of 23 patients with metastatic disease. CETCs were determined using the maintrac® method. Gene expression profiles of single CETCs and tumorspheres of the same patients were analyzed using qRT-PCR.
  
  
  RESULTS
  Sphere formation was observed in 79 % of patients. We found that the number of tumorspheres depended on stage of disease. Furthermore, the most important factor for growing of tumorspheres is obtaining chemotherapy. Patients with chemotherapy treatment had lower numbers of tumorspheres compared to patients without chemotherapy. Patients with HER2 positive primary tumor had higher number of tumorspheres. Analysis of surface marker expression profile of tumorspheres showed that cells in the spheres had typical phenotype of cancer stem cells. There was no sphere formation in a control group with 50 healthy donors.
  
  
  CONCLUSIONS
  This study demonstrates that a small fraction of CETCs has proliferative activity. Identifying the CETC subset with cancer stem cell properties may provide more clinically useful prognostic information. Chemotherapy is the most important component in cancer therapy because it frequently reduces the number of tumorspheres.
authors.affiliation: Transfusion Center Bayreuth, 95448, Bayreuth, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Pizon
authors.affiliation: Transfusion Center Bayreuth, 95448, Bayreuth, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Schott
authors.affiliation: Transfusion Center Bayreuth, 95448, Bayreuth, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pachmann
authors.affiliation: Transfusion Center Bayreuth, 95448, Bayreuth, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pachmann
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
keywords: breast cancer; circulating cancer stem cells; circulating epithelial tumor cells; predictor for presence of metastasis