title: Progestin treatment decreases CD133+ cancer stem cell populations in endometrial cancer.
abstract: OBJECTIVE
  Endometrial cancer is a hormonally responsive malignancy. Response to progestins is associated with estrogen receptor (ER) and progesterone receptor (PR) status. CD133 is a marker of endometrial cancer stem cells. We postulated that CD133+ cells express ER and PR and that progestin therapy differentially regulates CD133+ cells.
  
  
  METHODS
  The Ishikawa (ER/PR positive) and KLE (ER/PR negative) cell lines were examined for the presence of CD133 populations. Cell lines were treated with 30.4μM medroxyprogesterone 17-acetate (MPA) for 6days. After treatment, cell counts, apoptosis assays and CD133+ populations were examined. In a clinical project, we identified 12 endometrial cancer patients who were treated with progestin drugs at our institution. Using immunohistochemistry, CD133, ER, PR, and androgen receptor (AR) expression was scored and evaluated for change over time on serial biopsies.
  
  
  RESULTS
  CD133+ populations were identified in Ishikawa and KLE cell lines. MPA treatment resulted in a significant reduction in the percentage of live cells (Ishikawa, P=0.036; KLE, P=0.0002), significant increase in apoptosis (Ishikawa, P=0.01; KLE, P=0.0006) and significant decrease in CD133+ populations (Ishikawa, P<0.0001; KLE, P=0.0001). ER, PR, AR and CD133 were present in 96.4%, 96.4%, 89.3% and 100% of patient samples respectively. Paralleling the in vitro results, CD133 expression decreased in patients who had histologic response to progestin treatment.
  
  
  CONCLUSIONS
  CD133+ populations decreased after treatment with MPA in an in vitro model and in patients responding to treatment with progestins. Progestin treatment differentially decreases CD133+ cells.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine, Cincinnati, OH 45219, USA. Electronic address: michael.s.guy@gmail.com.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Guy
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Lubna
authors.initials: L
authors.lastname: Qamar
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Kian
authors.initials: K
authors.lastname: Behbakht
authors.affiliation: Department of Pathology, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
authors.forename: Miriam D
authors.initials: MD
authors.lastname: Post
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Sheeder
authors.affiliation: Department of Pathology, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Sartorius
authors.affiliation: Texas Oncology, Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA.
authors.forename: Monique A
authors.initials: MA
authors.lastname: Spillman
mesh_terms: D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018931:Antineoplastic Agents, Hormonal; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017258:Medroxyprogesterone Acetate
keywords: Cancer stem cells; Endometrial cancer; Hormonal treatment; Progesterone; Progestin