Colocalization of basal and luminal cell-type cytokeratins in human prostate cancer.
In the epithelium of secretory acini of the prostate two different cell types can be discriminated on the basis of localization, morphology, and degree of differentiation, the luminal and basal cells. The possibility of a developmental relationship between basal and luminal cells has been a subject of interest in several studies. According to the stem cell model at least three cell types, i.e., stem, amplifying, and transit cells, can be discriminated in the epithelium of prostate secretory acini. We previously reported that in the process of degeneration and regeneration in normal rat prostate a population of cells could be identified as candidates for the amplifying cells. These cells showed a keratin expression profile intermediate between those of basal and luminal cells. We now show, by using keratin antibodies, that also in normal human prostate at least three subpopulations of cells can be identified, one of them putatively representing amplifying cells as defined in the stem cell model. Furthermore, these antibodies were used to obtain a better insight into the different cell types involved in the etiology and progression of prostatic carcinoma. Both primary and hormone-independent prostatic tumors were investigated. Our results indicated that the candidate stem cell population was absent in prostatic carcinoma. Unlike earlier reports on the unique presence of cells with luminal characteristics in prostatic carcinoma, we identified also a population of cells coexpressing basal and luminal cell-type cytokeratins in primary and hormone-independent prostatic carcinoma. Since amplifying cells are defined in the stem cell model as precursors of transit (luminal) cells in the hierarchical pathway of prostatic epithelium differentiation, we postulate that on the basis of the keratin expression profile this subpopulation is most likely the target for neoplastic transformation.
Verhagen
A P
AP
Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Ramaekers
F C
FC
Aalders
T W
TW
Schaafsma
H E
HE
Debruyne
F M
FM
Schalken
J A
JA
D000911:Antibodies, Monoclonal; D002280:Basal Cell Carcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D006801:Humans; D015151:Immunoblotting; D016130:Immunophenotyping; D007633:Keratins / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*
D000911:Antibodies, Monoclonal; D007633:Keratins