The prostatic cellular and molecular kaleidoscope. Starting points for carcinogenesis

Vol. 59 No. 1, 2018

ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Andrei Daniel Timofte, Irina-Draga Caruntu

The prostate cancer is a heterogeneous disorder concealing different phenotypical and functional subtypes of cancer cells. This heterogeneity mirrors the normal prostate cell lineages whose alterations represent the starting points of the carcinogenesis mechanism. The histological structure of the prostate comprises two main types of cells: epithelial and stromal, with a stromal to epithelial ratio of 2:1. The prostate acini are lined by a contiguous layer composed of four different subtypes of epithelial cells: secretory luminal, basal, neuroendocrine, and transit-amplifying. The epithelial component is enclosed in a stromal tissue, consisting of several types of cells: smooth muscle cells (the most numerous cell type), fibroblasts, and myofibroblasts. Despite their quite similar morphological appearance in light microscopy, the molecular markers expressed by the normal epithelial and stromal prostatic components, as well as the stem cells show that the prostatic cells are not equal. Numerous efforts have been made to identify the profile of prostate stem cells, and their role in cellular turnover and morphogenesis of the prostatic tissue, by using experimental and/or human studies. Consequently, several hypotheses regarding the location and the phenotype of these cells were formulated and tested, mainly in animal models. The molecular mapping of normal human prostate tissue might be the key for unlocking the intricate mechanisms of prostate carcinogenesis. Within this context, the prostatic cancer stem cells are thought to play an important role in tumor initiation, progression, recurrence and also therapy resistance. The cancerous phenotype of a stem cell can be reached via multiple genetic trajectories and epigenetic alterations, resulting in different subclonal populations of cancer stem cells, thus explaining the heterogeneity of the prostatic neoplasia. Future efforts should be directed towards better understanding of the relationship and interactions between these cancer stem cells subpopulations, their microenvironments, and also towards characterizing the signaling pathways and molecules involved in the regulation of prostatic cancer stem cells. The results of these studies could offer a different, more comprehensible perspective for a new, molecular classification of prostate cancer, overlapping the existing histological one.

Corresponding author: Irina-Draga Caruntu, Professor, MD, PhD; e-mail: irinadragacaruntu@gmail.com

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