title: Human uterine leiomyoma stem/progenitor cells expressing CD34 and CD49b initiate tumors in vivo.
abstract: BACKGROUND
  Uterine leiomyoma is the most common benign tumor in reproductive-age women. Using a dye-exclusion technique, we previously identified a side population of leiomyoma cells exhibiting stem cell characteristics. However, unless mixed with mature myometrial cells, these leiomyoma side population cells did not survive or grow well in vitro or in vivo.
  
  
  OBJECTIVE
  The objective of this study was to identify cell surface markers to isolate leiomyoma stem/progenitor cells.
  
  
  METHODS
  Real-time PCR screening was used to identify cell surface markers preferentially expressed in leiomyoma side population cells. In vitro colony-formation assay and in vivo tumor-regeneration assay were used to demonstrate functions of leiomyoma stem/progenitor cells.
  
  
  RESULTS
  We found significantly elevated CD49b and CD34 gene expression in side population cells compared with main population cells. Leiomyoma cells were sorted into three populations based on the expression of CD34 and CD49b: CD34(+)/CD49b(+), CD34(+)/CD49b(-), and CD34(-)/CD49b(-) cells, with the majority of the side population cells residing in the CD34(+)/CD49b(+) fraction. Of these populations, CD34(+)/CD49b(+) cells expressed the lowest levels of estrogen receptor-α, progesterone receptor, and α-smooth muscle actin, but the highest levels of KLF4, NANOG, SOX2, and OCT4, confirming their more undifferentiated status. The stemness of CD34(+)/CD49b(+) cells was also demonstrated by their strongest in vitro colony-formation capacity and in vivo tumor-regeneration ability.
  
  
  CONCLUSIONS
  CD34 and CD49b are cell surface markers that can be used to enrich a subpopulation of leiomyoma cells possessing stem/progenitor cell properties; this technique will accelerate efforts to develop new therapies for uterine leiomyoma.
authors: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology (P.Y., M.O., M.B.M., J.S.C.V., A.N., D.M., M.T.D., S.A.D., S.S.M., W.Q., D.C., J.J.K., S.E.B.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611; and Department of Molecular and Cellular Biochemistry (V.A.S.), The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210.
authors: Ping
authors: P
authors: Yin
authors: Masanori
authors: M
authors: Ono
authors: Molly B
authors: MB
authors: Moravek
authors: John S
authors: JS
authors: Coon
authors: Antonia
authors: A
authors: Navarro
authors: Diana
authors: D
authors: Monsivais
authors: Matthew T
authors: MT
authors: Dyson
authors: Stacy A
authors: SA
authors: Druschitz
authors: Saurabh S
authors: SS
authors: Malpani
authors: Vanida A
authors: VA
authors: Serna
authors: Wenan
authors: W
authors: Qiang
authors: Debabrata
authors: D
authors: Chakravarti
authors: J Julie
authors: JJ
authors: Kim
authors: Serdar E
authors: SE
authors: Bulun
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation / Q000379:methods; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D039421:Integrin alpha2; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4