title: Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance.
abstract: OBJECTIVE
  Adipose tissue contains a population of multipotent adipose stem cells (ASCs) that form tumor stroma and can promote tumor progression. Given the high rate of ovarian cancer metastasis to the omental adipose, we hypothesized that omental-derived ASC may contribute to ovarian cancer growth and dissemination.
  
  
  METHODS
  We isolated ASCs from the omentum of three patients with ovarian cancer, with (O-ASC4, O-ASC5) and without (O-ASC1) omental metastasis. BM-MSCs, SQ-ASCs, O-ASCs were characterized with gene expression arrays and metabolic analysis. Stromal cells effects on ovarian cancer cells proliferation, chemoresistance and radiation resistance was evaluated using co-culture assays with luciferase-labeled human ovarian cancer cell lines. Transwell migration assays were performed with conditioned media from O-ASCs and control cell lines. SKOV3 cells were intraperitionally injected with or without O-ASC1 to track in-vivo engraftment.
  
  
  RESULTS
  O-ASCs significantly promoted in vitro proliferation, migration chemotherapy and radiation response of ovarian cancer cell lines. O-ASC4 had more marked effects on migration and chemotherapy response on OVCA 429 and OVCA 433 cells than O-ASC1. Analysis of microarray data revealed that O-ASC4 and O-ASC5 have similar gene expression profiles, in contrast to O-ASC1, which was more similar to BM-MSCs and subcutaneous ASCs in hierarchical clustering. Human O-ASCs were detected in the stroma of human ovarian cancer murine xenografts but not uninvolved ovaries.
  
  
  CONCLUSIONS
  ASCs derived from the human omentum can promote ovarian cancer proliferation, migration, chemoresistance and radiation resistance in-vitro. Furthermore, clinical O-ASCs isolates demonstrate heterogenous effects on ovarian cancer in-vitro.
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Aleksandra
authors: A
authors: Nowicka
authors: Frank C
authors: FC
authors: Marini
authors: Travis N
authors: TN
authors: Solley
authors: Paula B
authors: PB
authors: Elizondo
authors: Yan
authors: Y
authors: Zhang
authors: Hadley J
authors: HJ
authors: Sharp
authors: Russell
authors: R
authors: Broaddus
authors: Mikhail
authors: M
authors: Kolonin
authors: Samuel C
authors: SC
authors: Mok
authors: Melissa S
authors: MS
authors: Thompson
authors: Wendy A
authors: WA
authors: Woodward
authors: Karen
authors: K
authors: Lu
authors: Bahar
authors: B
authors: Salimian
authors: Deepak
authors: D
authors: Nagrath
authors: Ann H
authors: AH
authors: Klopp
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009852:Omentum / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D059467:Transcriptome