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

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.