title: Human adipose-derived mesenchymal stromal cell pigment epithelium-derived factor cytotherapy modifies genetic and epigenetic profiles of prostate cancer cells.
abstract: OBJECTIVE
  Adipose-derived mesenchymal stromal cells (ASCs) are promising tools for delivery of cytotherapy against cancer. However, ASCs can exert profound effects on biological behavior of tumor cells. Our study aimed to examine the influence of ASCs on gene expression and epigenetic methylation profiles of prostate cancer cells as well as the impact of expressing a therapeutic gene on modifying the interaction between ASCs and prostate cancer cells.
  
  
  METHODS
  ASCs were modified by lentiviral transduction to express either green fluorescent protein as a control or pigment epithelium-derived factor (PEDF) as a therapeutic molecule. PC3 prostate cancer cells were cultured in the presence of ASC culture-conditioned media (CCM), and effects on PC3 or DU145. Ras cells were examined by means of real-time quantitative polymerase chain reaction, EpiTect methyl prostate cancer-focused real-time quantitative polymerase chain reaction arrays, and luciferase reporter assays.
  
  
  RESULTS
  ASCs transduced with lentiviral vectors were able to mediate expression of several tumor-inhibitory genes, some of which correlated with epigenetic methylation changes on cocultured PC3 prostate cancer cells. When PC3 cells were cultured with ASC-PEDF CCM, we observed a shift in the balance of gene expression toward tumor inhibition, which suggests that PEDF reduces the potential tumor-promoting activity of unmodified ASCs.
  
  
  CONCLUSIONS
  These results suggest that ASC-PEDF CCM can promote reprogramming of tumor cells in a paracrine manner. An improved understanding of genetic and epigenetic events in prostate cancer growth in response to PEDF paracrine therapy would enable a more effective use of ASC-PEDF, with the goal of achieving safer yet more potent anti-tumor effects.
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Zolochevska
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Shearer
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Jayne
authors.initials: J
authors.lastname: Ellis
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Fokina
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Forum
authors.initials: F
authors.lastname: Shah
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address: mlfiguei@utmb.edu.
authors.forename: Marxa L
authors.initials: ML
authors.lastname: Figueiredo
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D063646:Carcinogenesis / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000628:therapy*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche; D059467:Transcriptome; D019076:Transgenes / Q000235:genetics; D014407:Tumor Cells, Cultured; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
keywords: adipose-derived mesenchymal stromal cells; epigenetics; gene expression; pigment epithelium–derived factor; prostate cancer