Abstract
The female reproductive system (FRS) has a great capacity for regeneration. The existence of somatic stem cells (SSC) that are likely to reside in distinct tissue compartments of the FRS is anticipated. Normal SSC are capable of regenerating themselves, produce a progeny of cells that differentiate and maintain tissue architecture and functional characteristics, and respond to homeostatic controls. Among those SSC of the FRS that have been identified are: a) undifferentiated cells capable of differentiating into thecal cells and synthesizing hormones upon transplantation, b) ovarian surface epithelium stem cells, mitotically responsive to ovulation, c) uterine endometrial and myometrial cells, as clonogenic epithelial and stromal cells, and d) epithelial and mesenchymal cells with self-renewal capacity and multipotential from cervical tissues. Importantly, these cells are believed to significantly contribute to the development of different pathologies and tumors of the FRS.It is now widely accepted that cancer stem cells (CSC) are at the origin of many tumors. They are capable of regenerating themselves, produce a progeny that will differentiate aberrantly and do not respond adequately to homeostatic controls. Several cell surface antigens such as CD44, CD117, CD133 and MYD88 have been used to isolate ovarian cancer stem cells. Clonogenic epithelial and stromal endometrial and myometrial cells have been found in normal and cancer tissues, as side population, label-retaining cells, and CD146/PDGF-R beta-positive cells with stem-like features. In summary, here we describe a number of studies supporting the existence of somatic stem cells in the normal tissues and cancer stem cells in tumors of the human female reproductive system.
Highlights
Somatic stem cells (SSC) share three common features; i) generate identical cells retaining this capacity over long periods, ii) produce a progeny that differentiates into mature cells exhibiting specialized functions, iii) respond to homeostatic controls regulating decision to self renew or produce differentiating progenitors
We present evidences based in an extensive description of markers expression and functional assays (Table 2) supporting existence of both normal and cancer stem cells in the human FRS, as well as their role in the normal physiology and gynecological pathologies
Endometrial cancer stem cells Functional assays In a study of a uterine carcinosarcoma-derived cell line, colony-initiating cells grew for >50 serial passages and were composed of cells with columnar, small epithelial, moderately sized or large epithelial like, malignant tumor giant and spindle-shaped morphologies, similar to those found in the original cell line
Summary
Somatic stem cells (SSC) share three common features; i) generate identical cells retaining this capacity over long periods (referred as long-term self-renewal), ii) produce a progeny that differentiates into mature cells exhibiting specialized functions, iii) respond to homeostatic controls regulating decision to self renew or produce differentiating progenitors. Experimental strategies for isolation and identification of cancer stem cells, as well as major tumor types originating within the FRS together with genetic mutations and clinical treatments are shown (Table 1). We present evidences based in an extensive description of markers expression and functional assays (Table 2) supporting existence of both normal and cancer stem cells in the human FRS, as well as their role in the normal physiology and gynecological pathologies.
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