title: Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors.
abstract: OBJECTIVE
  Cancer stem cells represent an attractive therapeutic target for tumor eradication. The present study aimed to determine whether CD133 expression may identify cells with characteristics of cancer stem/progenitor cells in human endometrial tumors.
  
  
  METHODS
  We analyzed 113 tumor samples for CD133/1 expression by flow cytometry, immunohistochemistry, and semiquantitative reverse transcription-PCR. CD133(+) cells were isolated and used to assess phenotypic characteristics, self-renewal capacity, ability to maintain CD133 expression and form sphere-like structures in long-term cultures, sensitivity to chemotherapeutic agents, gene expression profile, and ability to initiate tumors in NOD/SCID mice.
  
  
  RESULTS
  Primary tumor samples exhibited a variable degree of immunoreactivity for CD133/1, ranging from 1.3% to 62.6%, but stained negatively for other endothelial and stem cell-associated markers. Isolated CD133(+) cells expanded up to 4.6-fold in serum-replenished cultures and coexpressed the GalNAcalpha1-O-Ser/Thr MUC-1 glycoform, a well-characterized tumor-associated antigen. Dissociated bulk tumors formed sphere-like structures; cells grown as tumor spheres maintained CD133 expression and could be propagated for up to 12 weeks. CD133(+) cells purified from endometrioid adenocarcinomas were resistant to cisplatin-induced and paclitaxel-induced cytotoxicity and expressed a peculiar gene signature consisting of high levels of matrix metalloproteases, interleukin-8, CD44, and CXCR4. When serially transplanted into NOD/SCID mice, CD133(+) cells were capable of initiating tumor formation and recapitulating the phenotype of the original tumor.
  
  
  CONCLUSIONS
  CD133 is expressed by human endometrial cancers and might represent a valuable tool to identify cells with cancer stem cell characteristics.
authors.affiliation: Department of Hematology and Department of Gynecology, Catholic University Medical School, USA. srutella@rm.unicatt.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bonanno
authors.forename: Annabella
authors.initials: A
authors.lastname: Procoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Mariotti
authors.forename: Maria
authors.initials: M
authors.lastname: Corallo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Prisco
authors.forename: Adriana
authors.initials: A
authors.lastname: Eramo
authors.forename: Chiara
authors.initials: C
authors.lastname: Napoletano
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Perillo
authors.forename: Marianna
authors.initials: M
authors.lastname: Nuti
authors.forename: Luca
authors.initials: L
authors.lastname: Pierelli
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse