Effects of transplantation of adipose tissue-derived stem cells on prostate tumor.
BACKGROUND
Obesity is a risk factor for prostate cancer development, but the underlying mechanism is unknown. The present study tested the hypothesis that stromal cells of the adipose tissue might be recruited by cancer cells to help tumor growth.


METHODS
PC3 prostate cancer cells were transplanted into the subcutaneous space of the right flank of athymic mice. One week later, adipose tissue-derived stromal or stem cells (ADSC) or phosphate-buffered saline (PBS, as control) was transplanted similarly to the left flank. Tumor size was monitored for the next 34 days; afterwards, the mice were sacrificed and their tumors harvested for histological examination. The ability of PC3 cells to attract ADSC was tested by migration assay. The involvement of the CXCL12/CXCR4 axis was tested by migration assay in the presence of a specific inhibitor AMD3100.


RESULTS
Throughout the entire course, the average size of PC3 tumors in ADSC-treated mice was larger than in PBS-treated mice. ADSC were identified inside the tumors of ADSC-treated mice; CXCR4 expression was also detected. Migration assay indicated the involvement of the CXCL12/CXCR4 axis in the migration of ADSC toward PC3 cells. Capillary density was twice as high in the tumors of ADSC-treated mice than in the tumors of PBS-treated mice. VEGF expression was similar but FGF2 expression was significantly higher in tumors of ADSC-treated mice than in the tumors of PBS-tread mice.


CONCLUSIONS
Prostate cancer cells recruited ADSC by the CXCL12/CXCR4 axis. ADSC helps tumor growth by increasing tumor vascularity, and which was mediated by FGF2.
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California 94143-0738, USA.
Guiting
G
Lin
Rong
R
Yang
Lia
L
Banie
Guifang
G
Wang
Hongxiu
H
Ning
Long-Cheng
LC
Li
Tom F
TF
Lue
Ching-Shwun
CS
Lin
D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D001596:Benzylamines; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000080027:Cyclams; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001596:Benzylamines; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2; C088327:plerixafor