The spermatogonial stem cell niche in testicular germ cell tumors

Abstract

Spermatogonial stem cells (SSCs) are pluripotent elements found in the adult seminiferous epithelium between Sertoli cells and a basal lamina which covers the multilayered external wall of peritubular myoid cells. The microenvironment of this pluripotent stem cell niche creates the complex and dynamic system that is necessary for the initiation of spermatogenesis, but this system also contains factors which can potentially collaborate in the progression of testicular germ cell tumors (TGCTs). In this review, we summarize our current knowledge about some important structural and molecular features related to the SSC niche, including growth factors, adhesion molecules, extracellular matrix, mechanical stress and vascularization. We discuss their possible collaborative effects on the generation and progression of TGCTs, which are a type of cancer representing the most frequent neoplasia among young men and whose incidence has grown very quickly during the past decades in North America and Europe. In this regard, a better understanding of the pluripotent stem cell niche where these malignancies arise will provide further insights into the origin of TGCTs and the mechanisms underlying their growth and invasion of adjacent and distant tissues.

An oncofetal and developmental perspective on testicular germ cell cancer

“…PGCs at genital ridge are called gonocytes and further mature into oogonia and spermatogonia [2,[42][43][44] under strict regulation of the genomic constitution (XX vs XY) and the (gonadal) micro-environment. In an XX constitution the transcription factor SRY will be expressed leading to SOX9 expression and the formation of Sertoli cells: the supporting cells in the testis that guide gonocytes into maturation along the male germ cell lineage [60][61][62][63]. If SRY is not (sufficiently) expressed (physiological in XY condition), granulosa cells will be formed instead which, in the presence of e.g.…”

A Novel Feeder-Free Culture System for Expansion of Mouse Spermatogonial Stem Cells

“…In vitro propagation of SSCs requires glial cell line-derived neurotrophic factor (GDNF) (Kubota et al, 2004; Ryu et al, 2005), which is secreted from Sertoli cells for maintenance of SSCs in the testis (Meng et al, 2000), as well as other growth factors, such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) are required for in vitro propagation of SSCs (Kubota et al, 2004; Rastegar et al, 2013). In general, physical interaction of SSCs with the basal epithelial membrane is required to provide a microniche for self-renewing (Oatley and Brinster, 2012; Phillips et al, 2010; Ryu et al, 2006; Silvan et al, 2013). When primary SSCs are derived from the testis and proliferated in vitro , mouse embryonic fibroblasts (MEFs) are the most commonly used feeder cells that play a role of such microniche by allowing secure attachment and proliferation of SSCs.…”

Inhibitory effect of <i>Taraxacum officinale</i> L (Compositae) aqueous root extract on spermatogenesis

“…A nonsense mutation in plzf gene showed defective spermatogenic self-renewal [29]. Silvan et al [30] reported that MCSF interacts with GDNF and acts specifically on undifferentiated SSCs and that its effect causes spermatogonia self-renewal rather than differentiation.…”