Peritubular myoid cell‐derived factors and its potential role in the progression of testicular germ cell tumours

Abstract

The tumour surrounding stroma, known as reactive stroma, is a crucial factor to understand cancer cell growth and invasion. In the normal adult testis, the stroma contains extracellular matrix components, fibroblasts, infiltrating leucocytes, lymphocytes, macrophages and capillaries, as well as other specific cell populations, like Leydig cells and a thin myoepithelium surrounding the seminiferous tubules constituted by the peritubular cells. All these cells are an important source of proliferation and survival promoting signals, proteolytic enzymes, migratory cues and pro-angiogenic factors. Ascribable to this pro-invasive activity, the tumour reactive stroma cells, especially cancer-associated myofibroblasts, have emerged as a promising target for cancer therapy. This review is focused on the potential role of the peritubular myoid cells in the development of testicular germ cell tumours as the precursors of cancer-associated myofibroblast and on an experimental model for the study of testis germinal cancer stroma and on the differences between normal and tumour-associated stromal cells, including the molecular mechanisms that mediate the important cancer stroma crosstalk. Special attention will be paid to the cancer-associated myofibroblasts as possible therapeutic targets, because they are one of the main components of the reactive stroma and are known to secrete a variety of paracrine factors that stimulate tumour progression.

Human testicular peritubular cells: more than meets the eye

“…Answers to an old question, whether the peritubular cell population may contain Leydig cell progenitor or even stem cells, as implied by several studies in rodents, may be provided. Finally, the study of human peritubular cells may help to clarify their potential contribution to germ cell tumor development and progression, which is an emerging topic of clinical relevance (Diez-Torre et al 2011). …”

Primary Human Testicular Cells Self-Organize into Organoids with Testicular Properties

“…We show here that a number of in vivo testicular processes related to ECM (including the blood-testis barrier) remodeling were recapitulated in TOs derived from both young and adult cells (Díez-Torre et al., 2011, Mruk and Cheng, 2004, Siu and Cheng, 2004). First, tumor necrosis factor alpha, tissue inhibitor of metalloproteinase 1, IL-6, and monocyte chemotactic protein 1 were produced, as detected by way of membrane antibody arrays.…”

The Male Germinal Stem Cell Niche in Mammals

“…7 cKITr (upper row) and LIFr (lower row) fluorescent immunohistochemistry revealed the presence of these receptors in the most undifferentiated cells of the seminiferous epithelium (in red), being practically absent in more differentiated cells (blue signal corresponds to nuclear DAPI staining). Scale bar: 25 µm myofibroblasts [11], a cell population known to participate in the development of tumors. It is therefore becoming increasingly important to understand the mechanisms by which the cell types present in the testis maintain and regulate SSC renewal and differentiation.…”