title: Increased expression of putative cancer stem cell markers in the bone marrow of prostate cancer patients is associated with bone metastasis progression.
abstract: BACKGROUND
  The number of cells positive for the α-6 and α-2 integrin subunits and the c-Met receptor in primary tumors and bone biopsies from prostate cancer patients has been correlated with metastasis and disease progression. The objective of this study was to quantify disseminated tumour cells present in bone marrow in prostate cancer patients using specific markers and determine their correlation with metastasis and survival.
  
  
  METHODS
  Patients were included at different stage of prostate cancer disease, from localised to metastatic castration-resistant prostate cancer. Healthy men were used as a control group. Bone marrow samples were collected and nucleated cells separated. These were stained for CD45, α-2, α-6 integrin subunits and c-Met and samples were processed for analysis and quantification of CD45-/α2+/α6+/c-met + cells using flow cytometry. Clinical and pathological parameters were assessed and survival measured. Statistical analyses were made of associations between disease specific parameters, bone marrow flow cytometry data, prostate-specific antigen (PSA) progression free survival and bone metastases progression free survival.
  
  
  RESULTS
  For all markers, the presence of more than 0.1% positive cells in bone marrow aspirates was significantly associated with the risk of biochemical progression, the risk of developing metastasis and death from prostate cancer.
  
  
  CONCLUSIONS
  Quantification of cells carrying putative stem cell markers in bone marrow is a potential indicator of disease progression. Functional studies on isolated cells are needed to show more specifically their property for metastatic spread in prostate cancer.
authors.affiliation: Service d'Urologie et Chirurgie de la Transplantation, Université Lyon 1, Lyon, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Ricci
authors.forename: Eve
authors.initials: E
authors.lastname: Mattei
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Colby L
authors.initials: CL
authors.lastname: Eaton
authors.forename: Freddy
authors.initials: F
authors.lastname: Hamdy
authors.forename: Gabri
authors.initials: G
authors.lastname: van der Pluije
authors.forename: Marco
authors.initials: M
authors.lastname: Cecchini
authors.forename: George
authors.initials: G
authors.lastname: Thalmann
authors.forename: Philippe
authors.initials: P
authors.lastname: Clezardin
authors.forename: Marc
authors.initials: M
authors.lastname: Colombel
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D001859:Bone Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D039421:Integrin alpha2; D039503:Integrin alpha6; D019859:Proto-Oncogene Proteins c-met; D017493:Leukocyte Common Antigens
keywords: bone metastasis; c-Met; disseminated tumor cells; prostate cancer; α-2 integrin subunit; α-6 integrin subunit