Tumor-promoting phenotype of CD90hi prostate cancer-associated fibroblasts.
BACKGROUND
Cancer-associated stroma contributes to the malignant behavior of adenocarcinomas of the prostate and other organs. CD90 is a marker of mesenchymal stem cells (MSCs) and its expression is higher in prostate cancer stroma compared to normal tissue. Cultured prostate cancer-associated fibroblasts (CAFs) expressing high versus low levels of CD90 were analyzed for an MSC-like or tumor-promoting phenotype.


METHODS
CD90(hi) and CD90(lo) cells were collected by fluorescence-activated cell sorting (FACS). Expression of genes associated with MSCs and/or tumor-promoting activities was measured by quantitative polymerase chain reaction (qPCR). Effects of stromal cell co-culture or conditioned media were tested on BPH-1 epithelial cells.


RESULTS
The pattern of gene expression did not support the hypothesis that CD90(hi) cells were MSCs. However, CD90(hi) cells expressed higher levels of many genes associated with tumor promotion, including cytokines, angiogenic factors, hedgehog signaling components, and transforming growth factor (TGF)-beta. Co-culture or conditioned medium from CD90(hi) cells increased CXCR4 expression in BPH-1 cells, at least in part due to TGF-beta, and protected BPH-1 cells from apoptosis.


CONCLUSIONS
Our results suggest that the elevated expression of CD90 previously observed in the cancer-associated stroma of the human prostate is biologically significant. Although our results do not support the idea that CD90(hi) cells cultured from the cancer stroma are MSCs, our findings suggest that the phenotype of these cells is more tumor-promoting than that of cells expressing low CD90.
Zhao
Hongjuan
H
Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5118, USA.
Peehl
Donna M
DM
D000368:Aged; D002450:Cell Communication / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology; D008875:Middle Aged; D016877:Oxidants / Q000494:pharmacology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D050794:STAT1 Transcription Factor / Q000502:physiology; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology*; D018800:Thy-1 Antigens / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
D017077:Culture Media, Conditioned; D053823:Hedgehog Proteins; D016877:Oxidants; D050794:STAT1 Transcription Factor; D018800:Thy-1 Antigens; D016212:Transforming Growth Factor beta; D006861:Hydrogen Peroxide