Cell-cell interaction in prostate gene regulation and cytodifferentiation.
To examine the role of intercellular interaction on cell differentiation and gene expression in human prostate, we separated the two major epithelial cell populations and studied them in isolation and in combination with stromal cells. The epithelial cells were separated by flow cytometry using antibodies against differentially expressed cell-surface markers CD44 and CD57. Basal epithelial cells express CD44, and luminal epithelial cells express CD57. The CD57+ luminal cells are the terminally differentiated secretory cells of the gland that synthesize prostate-specific antigen (PSA). Expression of PSA is regulated by androgen, and PSA mRNA is one of the abundant messages in these cells. We show that PSA expression by the CD57+ cells is abolished after prostate tissue is dispersed by collagenase into single cells. Expression is restored when CD57+ cells are reconstituted with stromal cells. The CD44+ basal cells possess characteristics of stem cells and are the candidate progenitors of luminal cells. Differentiation, as reflected by PSA production, can be detected when CD44+ cells are cocultured with stromal cells. Our studies show that cell-cell interaction plays an important role in prostatic cytodifferentiation and the maintenance of the differentiated state.
Liu
A Y
AY
Department of Urology, University of Washington, Seattle, WA 98195, USA. aliu@u.washington.edu
True
L D
LD
LaTray
L
L
Nelson
P S
PS
Ellis
W J
WJ
Vessella
R L
RL
Lange
P H
PH
Hood
L
L
van den Engh
G
G
D000728:Androgens / Q000502:physiology; D018959:CD57 Antigens / Q000276:immunology; D002454:Cell Differentiation; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D008297:Male; D011467:Prostate / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
D000728:Androgens; D018959:CD57 Antigens; D018960:Hyaluronan Receptors; D017430:Prostate-Specific Antigen