title: Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
abstract: BACKGROUND
  Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC) spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC) on pancreatic tumor cell proliferation.
  
  
  RESULTS
  Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate). ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth.
  
  
  CONCLUSIONS
  These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.
authors.affiliation: Université de Toulouse, UPS, UMR 5241 Métabolisme, Plasticité et Mitochondrie, BP 84225, Toulouse, France. beatrice.cousin@inserm.fr
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cousin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ravet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Poglio
authors.forename: Fabienne
authors.initials: F
authors.lastname: De Toni
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bertuzzi
authors.forename: Hubert
authors.initials: H
authors.lastname: Lulka
authors.forename: Ismahane
authors.initials: I
authors.lastname: Touil
authors.forename: Mireille
authors.initials: M
authors.lastname: André
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Grolleau
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Péron
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Chavoin
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourin
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Louis
authors.initials: L
authors.lastname: Buscail
authors.forename: Pierre
authors.initials: P
authors.lastname: Cordelier
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016193:G1 Phase; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D017077:Culture Media, Conditioned