Prostate cancer is a complex diease process, involving genetic, hormonal, and other epigenetic factors. Despite its clinical magnitude and the recent progress made in molecular biology, the pathogenesis of prostate cancer remains poorly understood. This reflects a number of factors including:
1. The complex composition of the prostate gland by different anatomic, cellular and functional compartments
2. The heterogeneous and multifocal nature of prostate cancer.
3. The limited number of estabilished cell lines for in vitro studies
4. The lack of suitable animal models that faithfully recapitulate all stages of disease progression.
The present review focuses on current morphogenetic factors implicated in the depelopment of prostate cancer and tumor progression. The concepts discussed below refer to recent data obtained in human prostate tissue.
The Cellular Biology of the Prostatci Epithelium
The prostatic epithelium has a complex composition by three cell types differenting in their hormonal regulation and marker expression (FIg.1.1) the most prevalent phnotype consists of secretory luminal cells expressing prostate spesific antigen (PSA) and cytokeratins 8 and 18[35,41]. Basal cells, the second most important phenotype, mediate attachment to the stroma and express high molecular weight cytokeratins [2,39,40]. The third phenotype shos neuroen-docrine (NE) differentiation. NE cells express chromogranins and secrete a number of neurosecretory products which may have growth promoting properties [26,27]. Although these basic cell types clearly differ ini their market expression and biological functions, they obviously share a common origin from pluripotent stem cells located in the basal cell layer [2,6,7]. This concept is based on the occurrence of intermediate differentiation among the tree properties of basal cells [2,6,7]. Cell kinetic studies indicate that the proliferation compartmen of the normal of hyperplastic epithelium is located in the basal cell player[14]. Seventy percent of proliferating epithelium is located in the basal cell specific cytokeratins, while the remaining 30% of cycling cells are identified in secretory luminal cell types [14]. Chromogranin A positive NE cells lack proliferative activity and represent a terminal differentiated cell population within the prostatic epithelial cell systems [8,16]. It is therefore most unlikely that NE cells present in the normal or dysplastic epithelium are precursors of prostate cancer cells, even those with NE features [4].
1. The complex composition of the prostate gland by different anatomic, cellular and functional compartments
2. The heterogeneous and multifocal nature of prostate cancer.
3. The limited number of estabilished cell lines for in vitro studies
4. The lack of suitable animal models that faithfully recapitulate all stages of disease progression.
The present review focuses on current morphogenetic factors implicated in the depelopment of prostate cancer and tumor progression. The concepts discussed below refer to recent data obtained in human prostate tissue.
The Cellular Biology of the Prostatci Epithelium
The prostatic epithelium has a complex composition by three cell types differenting in their hormonal regulation and marker expression (FIg.1.1) the most prevalent phnotype consists of secretory luminal cells expressing prostate spesific antigen (PSA) and cytokeratins 8 and 18[35,41]. Basal cells, the second most important phenotype, mediate attachment to the stroma and express high molecular weight cytokeratins [2,39,40]. The third phenotype shos neuroen-docrine (NE) differentiation. NE cells express chromogranins and secrete a number of neurosecretory products which may have growth promoting properties [26,27]. Although these basic cell types clearly differ ini their market expression and biological functions, they obviously share a common origin from pluripotent stem cells located in the basal cell layer [2,6,7]. This concept is based on the occurrence of intermediate differentiation among the tree properties of basal cells [2,6,7]. Cell kinetic studies indicate that the proliferation compartmen of the normal of hyperplastic epithelium is located in the basal cell player[14]. Seventy percent of proliferating epithelium is located in the basal cell specific cytokeratins, while the remaining 30% of cycling cells are identified in secretory luminal cell types [14]. Chromogranin A positive NE cells lack proliferative activity and represent a terminal differentiated cell population within the prostatic epithelial cell systems [8,16]. It is therefore most unlikely that NE cells present in the normal or dysplastic epithelium are precursors of prostate cancer cells, even those with NE features [4].
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