Role of the basal cells in premalignant changes of the human prostate: a stem cell concept for the development of prostate cancer

Abstract

Objectives: Prostatic intraepithelial neoplasias (PIN) result from abnormal differentiation and proliferation processes within the prostatic epithelial cell system. Recent data indicate that basal cells are essentially involved in normal and abnormal growth patterns of the human prostate.

Results: The basal cell layer represents the proliferative compartment and most probably houses the prostatic stem cell population. Basal cells are targets of several regulatory factors including estrogens, androgens, epidermal growth factor and other nonsteroidal growth factors. During the malignant transformation of the prostatic epithelium (PIN), the basal cell layer loses its proliferative function which is transferred to secretory luminal cell types. These proliferative abnormalities are attended by severe regulatory disorders of the programmed cell death within the prostatic epithelial cell system. The Bcl-2 oncoprotein which blocks the programmed cell death in the proliferative compartment (basal cell layer) in normal conditions, extends to the secretory luminal cell types in high-grade PIN lesions. This, in turn, may increase the genetic instability of the dysplastic epithelium. During the process of tumor invasion, the transformed cells lose their basal cell-specific phenotype and acquire features of exocrine cell types which represent the major phenotype in common prostate cancer. At the point of stromal invasion, the transformed cells produce neoplastic basement membrane material which allows them to penetrate the extracellular matrix.

Conclusion: These data provide theoretical bases for a stem cell concept in the development of prostate cancer and highlights the importance of basal cells in this multifactorial process.