BASAL CELLS ARE PROGENITORS OF LUMINAL CELLS IN PRIMARY CULTURES OF DIFFERENTIATING HUMAN PROSTATIC EPITHELIUM

BACKGROUND. Human prostatic epithelium consists mainly of basal and se cretory luminal cells: the origin of these phenotypes from a common st em cell, within the basal compartment, has been proposed but not yet d emonstrated. METHODS. Analyses by light and electron microscopy, immun ocytochemistry, and flow cytometry were used to determine lineage. The criteria for identifying the different phenotypes were characteristic morphology, and organization and expression of luminal- and basal-spe cific markers. RESULTS. After organoids attached, outgrowths appeared with cells maintaining close cell-to-cell associations. The dividing c ell compartment contained a subpopulation of cells with stem-cell char acteristics and a major population that may correspond to amplifying c ells. The characteristics of the stem-cell phenotype included reactivi ty with antibodies CKbasal, CK14, and Ki67. The amplifying cells were characterized as an intermediate phenotype between basal and luminal, as reactivity was demonstrated with CKbasal, CK14, and CK18. As outgro wths eventually merged, multilayering was apparent and cells on the up permost layer had numerous secretory vacuoles and reacted strongly wit h antibodies CK18 and CK19, androgen receptor, and prostate-specific a ntigen, which is characteristic of secretory luminal cells in vivo. In passaged cultures, loss of reactivity with CKbasal was detected; we p ostulate that this population contains the stem-cell fraction. CONCLUS IONS. These findings demonstrate that basal and luminal cells are of t he same lineage and are derived from a common stem cell. Moreover, the progenitor stem cells reside within the basal compartment. (C) 1998 W iley-Liss, Inc.