Increased expression of the adult stem cell marker Musashi‐1 in endometriosis and endometrial carcinoma

Abstract

Adult stem cells are thought to be responsible for the high regenerative capacity of the human endometrium, and have been implicated in the pathology of endometriosis and endometrial carcinoma. The RNA-binding protein Musashi-1 is associated with maintenance and asymmetric cell division of neural and epithelial progenitor cells. We investigated expression and localization of Musashi-1 in endometrial, endometriotic and endometrial carcinoma tissue specimens of 46 patients. qPCR revealed significantly increased Musashi-1 mRNA expression in the endometrium compared to the myometrium. Musashi-1 protein expression presented as nuclear or cytoplasmic immunohistochemical staining of single cells in endometrial glands, and of single cells and cell groups in the endometrial stroma. Immunofluorescence microscopy revealed colocalization of Musashi-1 with its molecular target Notch-1 and telomerase. In proliferative endometrium, the proportion of Musashi-1-positive cells in the basalis layer was significantly increased 1.5-fold in the stroma, and three-fold in endometrial glands compared to the functionalis. The number of Musashi-1 expressing cell groups was significantly increased (four-fold) in proliferative compared to secretory endometrium. Musashi-1 expressing stromal cell and cell group numbers were significantly increased (five-fold) in both endometriotic and endometrial carcinoma tissue compared to secretory endometrium. A weak to moderate, diffuse cytoplasmic glandular staining was observed in 50% of the endometriosis cases and in 75% of the endometrioid carcinomas compared to complete absence in normal endometrial samples. Our results emphasize the role of Musashi-1-expressing endometrial progenitor cells in proliferating endometrium, endometriosis and endometrioid uterine carcinoma, and support the concept of a stem cell origin of endometriosis and endometrial carcinoma.

Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues

“…Our data indicating an increased presence of stem cell markers in endometriotic samples are in agreement with the recent studies revealing an increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma (16). Our preliminary results indicate that the percentages of single cells positive for SALL4 and OCT4 we detected in the stroma of endometriotic tissues are comparable to those found by Gotte M et al for Musashi-1-positive cells (data not shown).…”

“…The presence of OCT4-and SALL4-positive cells mainly in the stroma of endometrial and endometriotic samples is in agreement with results of other studies based on stem cell detection through the analysis of stemness markers (38,16). Nevertheless, we found some SALL4-positive cells also in the vasculature and in periglandular positions.…”

“…Endometriosis can evolve into ovarian cancer (3,15) and other malignant diseases in which stem cells could play a role, as recently demonstrated (16). The relationship of endometriosis and ovarian cancer has been demonstrated both by epidemiological studies and by common genetic alterations (3).…”

The adult stem cell marker Musashi‐1 modulates endometrial carcinoma cell cycle progression and apoptosis via Notch‐1 and p21WAF1/CIP1

“…6 In endometrial carcinoma, the percentage of Musashi-1 expressing cells is significantly elevated as compared to healthy control endometrium. 7 Musashi-1 is an RNA-binding protein of 39 kD and was originally associated with maintenance and asymmetric cell division of neural and epithelial progenitor cells. 8 Its role in endometrial cancer induction and cancer progression is currently unknown, but several findings show its important role in tumor growth.…”

Sodium Butyrate Inhibits the Self-Renewal Capacity of Endometrial Tumor Side-Population Cells by Inducing a DNA Damage Response

“…Hubbard and colleagues showed that a small population of clonogenic cells from endometrial cancer tissues showed self-renewing, differentiating, and tumorigenic properties (14). Gotte and colleagues showed that the adult stem cell marker Musashi-1 was coexpressed with Notch-1 in a subpopulation of endometrial cells (15). Furthermore, they showed that telomerase and Musashi-1 expressing cells were significantly increased in proliferative endometrium, endometriosis, and endometrial carcinoma tissue, compared with secretary endometrium, suggesting the concept of a stem cell origin of endometriosis and endometrial carcinoma.…”