Role of CEACAM1 and CEACAM20 in an in vitro model of prostate morphogenesis.
CEACAM20, a novel member of the CEACAM1 gene family with expression limited to the lumen of small intestine, testes, and prostate, is co-expressed with CEACAM1 in adult prostate tissue and down-regulated to the same extent as CEACAM1 in prostate cancer. Since prostate cancer often involves loss of epithelial lumen formation, we hypothesized that CEACAM20 and CEACAM1 play important roles in lumen formation of normal prostate epithelium. When prostate cells were grown on Matrigel as a source of extracellular matrix (ECM), they differentiated into acinar structures with single tubules and well-defined lumina closely resembling embryonic prostate organoids. Confocal microscopic analysis revealed restriction of CEACAM20 to acini and CEACAM1 to tubule structures, respectively. Inhibition of CEACAM1 with antibodies or soluble CEACAM1 or antisense oligonucleotides inhibited tubule formation by over 50% while the remaining tubules were stunted. Inhibition of CEACAM20 with antisense oligonucleotides completely inhibited tubule formation and stunted the growth of acini. We conclude that CEACAM20 and CEACAM1 not only mark the lumina of adult prostate tissue but also play a critical role in the vitro generation of prostate organoids.
City of Hope Irell & Manella Graduate School of Biological Sciences, Duarte, California, USA.
Hui
H
Zhang
Andreas
A
Eisenried
Wolfgang
W
Zimmermann
John E
JE
Shively
D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008954:Models, Biological; D009024:Morphogenesis; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000166:cytology*; D011509:Proteoglycans
D015703:Antigens, CD; C069847:CD66 antigens; C583238:CEACAM20 protein, human; D015815:Cell Adhesion Molecules; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen