Stromal cell interplay in prostate development, physiology, and pathological conditions

Abstract

Advances in prostatic stroma studies over the past few decades have demonstrated that the stroma not only supports and nourishes the gland's secretory epithelium but also participates in key aspects of morphogenesis, in the prostate's hormonal metabolism, and in the functionality of the secretory epithelium. Furthermore, the stroma is implicated in the onset and progression of prostate cancer through the formation of the so‐called reactive stroma, which corresponds to a tumorigenesis‐permissive microenvironment. Prostatic stromal cells are interconnected and exchange paracrine signals among themselves in a gland that is highly sensitive to endocrine hormones. There is a growing body of evidence that telocytes, recently detected interstitial cells that are also present in the prostate, are involved in stromal organization, so that their processes form a network of interconnections with both the epithelium and the other stromal cells. The present review provides an update on the different types of prostate stromal cells, their interrelationships and implications for prostate development, physiology and pathological conditions.

The complex role of telocytes in female prostate tumorigenesis in a rodent model

“…However, in addition to the protective role that telocytes may play in the perialveolar muscle in the prostatic epithelium, it was found in both the control and the treated group that prostatic telocytes existed in close association with immune cells. This association has been verified in several other organs (Chi et al, 2015; Ibba‐Manneschi et al, 2016; Jiang et al, 2018; Wang et al, 2020), including the prostate (Sanches, Maldarine et al, 2021), in which telocytes produce proangiogenic factors and become sensitive to proinflammatory factors with aging (Sanches et al, 2020b). In the treated group, telocytes are also in the periphery of leukocyte infiltrates that occupy part of the interalveolar region.…”

“…Telocytes have been detected in the stroma of several organs and tissues such as the heart (Gherghiceanu & Popescu, 2012; Kostin, 2016), liver (J. Liu et al, 2016; Xiao et al, 2013), kidneys (Zheng et al, 2012), mammary glands (Petre et al, 2016; Sanches et al, 2020a), and testes (Liu, Liang et al, 2019; Marini et al, 2018), among others. Although there is no single function for these cells, their role in the organization of the stroma is especially notable (Sanches, Maldarine et al, 2021; Sanches Tamarindo et al, 2021). As in other organs, prostatic telocytes spread their telopodes throughout the stroma (Corradi et al, 2013).…”

“…As in other organs, prostatic telocytes spread their telopodes throughout the stroma (Corradi et al, 2013). These extensions connect the telocytes to each other and to other cell types, such as smooth muscle cells, fibroblasts, endothelial cells, nervous cells, and immune cells, among others (Sanches, Maldarine et al, 2021). In the prostate, as in the myocardium (Bani et al, 2010), digestive tract (Liang et al, 2019), uterus (Kagami et al, 2020; Roatesi et al, 2015), and other organs telocytes exist in close association with muscle cells.…”

“…In the prostate, there is evidence that telocytes contribute to angiogenesis and are sensitive to proinflammatory factors (Sanches et al, 2020b), which was also verified for lungs [69,70] and other organs (Manole et al, 2011; Mitrofanova et al, 2020). Regarding reactive stroma, it is interesting to note that there is an increase in the amount of CD34‐positive cells at the onset of stromal alterations (San Martin et al, 2014) and that these cells may be bone marrow–derived mesenchymal progenitor cells or even telocytes (Sanches, Maldarine et al, 2021).…”

Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer

“…Stroma mostly consists of fibroblasts and structural extracellular matrix (ECM) proteins, including collagens and laminins. In normal conditions, by releasing paracrine growth factors and under the androgen hormone influence, stroma cells nourish and orchestrate the physiologic development of the prostate gland, ensuing epithelial morphogenesis [ 2 ]. Analogously, prostate stroma components substantially cooperate in carcinogenic development by establishing a tumor-supportive environment [ 3 ].…”