Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
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.
Cousin
Beatrice
B
Université de Toulouse, UPS, UMR 5241 Métabolisme, Plasticité et Mitochondrie, BP 84225, Toulouse, France. beatrice.cousin@inserm.fr
Ravet
Emmanuel
E
Poglio
Sandrine
S
De Toni
Fabienne
F
Bertuzzi
Mélanie
M
Lulka
Hubert
H
Touil
Ismahane
I
André
Mireille
M
Grolleau
Jean-Louis
JL
Péron
Jean-Marie
JM
Chavoin
Jean-Pierre
JP
Bourin
Philippe
P
Pénicaud
Luc
L
Casteilla
Louis
L
Buscail
Louis
L
Cordelier
Pierre
P
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*
D017077:Culture Media, Conditioned