TGF-β and stem cell factor regulate cell proliferation in the proximal stem cell niche.
BACKGROUND
Stem cells are located in specific regulatory environments termed niches, which modulate the survival and proliferation of the cells through a variety of both mitogenic and inhibitory cytokines. In the murine prostate, stem cells are located in the proximal region of prostatic ducts. We examined the regulation of murine prostate cells in the stem cell niche by transforming growth factor beta (TGF-β) and stem cell factor (SCF).


METHODS
Prostate cells from the proximal and distal regions of prostatic ducts were cultured in the presence and absence of TGF-β and SCF, both on collagen-coated wells and in collagen gels. Cell growth on collagen was assessed by determining cell number. Cell growth in collagen gels was quantified by determining the number, size and complexity of prostatic ducts. The basal and luminal phenotype of the cells was determined by immunohistochemistry.


RESULTS
Endogenous TGF-β inhibited proliferation and promoted differentiation of proximal cells towards a luminal phenotype. It also inhibited duct-forming capacity and promoted differentiation of prostatic ducts towards a luminal phenotype. Addition of SCF enhanced proximal cell proliferation on collagen-coated wells and duct formation in collagen gels. Proliferation was further increased by ablation of endogenous TGF-β.


CONCLUSIONS
Proliferation and the basal/luminal cell composition of cells isolated from the proximal region of prostatic ducts, the stem cell niche, is regulated in part by opposing effects of SCF and endogenous TGF-β.
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Sarah
S
Salm
Patricia E
PE
Burger
Elaine Lynette
EL
Wilson
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D010641:Phenotype; D011467:Prostate / Q000166:cytology / Q000502:physiology; D051381:Rats; D019089:Stem Cell Factor / Q000502:physiology*; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta