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.
Highlights
Since multiple laboratories demonstrate that bone marrow-derived cells (BMDCs) take up long-term residence within the endometrium [14–17], we offer a novel perspective on how BMDCs within the tumor microenvironment may promote endometrial cancer stem cells (CSCs) survival and/or dormancy
BMDCs to the endometrium and introduced the concept that these cells may play a role in survival and dormancy of endometrial cancer cells (ECCs)
Detailed characterization of BMDCs is needed to better assess how different cell types homing to the endometrium may contribute to EC
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Type II EC pathogenesis is estrogen-independent, and tumors possess high metastatic potential, worsening patient prognosis and increasing cancer recurrence [6]. CSCs exhibit the hallmark properties of stem cells, including the ability to self-renew and to differentiate into progenitors [8] These cells resourcefully leverage their microenvironment to enter a dormant state, characterized by cell cycle quiescence, which confers resistance to treatment and immune evasion [9,10]. In EC the tumor microenvironment provides support to cancer cells via contact-dependent and/or contact-independent interactions, resulting in enhanced metastatic potential [13]. In this perspective article, we will discuss the function of various cell types within the EC microenvironment and their role in promoting EC progression. We leverage what is known about another sex hormone-driven cancer, breast cancer, in which the BM microenvironment plays a crucial role in acquisition of CSC phenotype and dormancy [18]
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