Bone Marrow-Derived Cells in Endometrial Cancer Pathogenesis: Insights from Breast Cancer

Abstract

Endometrial cancer is the most common gynecological cancer, representing 3.5% of all new cancer cases in the United States. Abnormal stem cell-like cells, referred to as cancer stem cells (CSCs), reside in the endometrium and possess the capacity to self-renew and differentiate into cancer progenitors, leading to tumor progression. Herein we review the role of the endometrial microenvironment and sex hormone signaling in sustaining EC progenitors and potentially promoting dormancy, a cellular state characterized by cell cycle quiescence and resistance to conventional treatments. We offer perspective on mechanisms by which bone marrow-derived cells (BMDCs) within the endometrial microenvironment could promote endometrial CSC (eCSC) survival and/or dormancy. Our perspective relies on the well-established example of another sex hormone-driven cancer, breast cancer, in which the BM microenvironment plays a crucial role in acquisition of CSC phenotype and dormancy. Our previous studies demonstrate that BMDCs migrate to the endometrium and express sex hormone (estrogen and progesterone) receptors. Whether the BM is a source of eCSCs is unknown; alternatively, crosstalk between BMDCs and CSCs within the endometrial microenvironment could be an additional mechanism supporting eCSCs and tumorigenesis. Elucidating these mechanisms will provide avenues to develop novel therapeutic interventions for EC.

Uterus: A Unique Stem Cell Reservoir Able to Support Cardiac Repair via Crosstalk among Uterus, Heart, and Bone Marrow

“…Indeed, BM-derived progenitor cells are involved in the post-partum remodeling of the uterus [ 102 , 103 ], as well as being able to repair damaged endometrium in a rat model [ 104 ]. With respect to pathological processes, one of the most popular theories for the etiology of endometriosis, the formation of endothelial tissue outside of its appropriate location in the uterus, has been owed to the trafficking of stem cells from the BM to other bodily sites, followed by differentiation of these cells into endometrial cells, at locations outside the uterus [ 105 ]. However, whether these findings are also applicable to humans, especially when accounting for the differences between mouse estrous and human menstruation periods, should be further investigated.…”

Circadian clock‐mediated nuclear receptors in cancer

“…ERs have two family members (ERα and ERβ), which belong to the nuclear receptor subfamily 3 group A. ERs play crucial roles in breast cancer, endometrial cancer, and osteoporosis (Ferrer et al, 2022; Jin et al, 2021; Wu et al, 2021). ERα expression and absence of ERβ expression are associated with a poorer prognosis in non‐small cell lung cancer.…”