Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
School of Graduate Studies Newark, Rutgers University, Newark, NJ 07103, USA.
Cells. 2022 Feb 17;11(4):714. doi: 10.3390/cells11040714.
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.
子宫内膜癌是最常见的妇科癌症，占美国所有新发癌症病例的 3.5%。异常的干细胞样细胞，称为癌症干细胞 (CSC)，存在于子宫内膜中，具有自我更新和分化为癌症前体的能力，导致肿瘤进展。本文综述了子宫内膜微环境和性激素信号在维持 EC 祖细胞并可能促进休眠中的作用，休眠是一种以细胞周期静止和对常规治疗耐药为特征的细胞状态。我们提供了关于骨髓来源细胞 (BMDC) 如何在子宫内膜微环境中促进子宫内膜 CSC (eCSC) 存活和/或休眠的观点。我们的观点依赖于另一种性激素驱动的癌症——乳腺癌的成熟范例，在乳腺癌中，BM 微环境在获得 CSC 表型和休眠中起着至关重要的作用。我们之前的研究表明，BMDC 迁移到子宫内膜并表达性激素（雌激素和孕激素）受体。BM 是否是 eCSC 的来源尚不清楚；或者，BMDC 与子宫内膜微环境中的 CSCs 之间的串扰可能是支持 eCSCs 和肿瘤发生的另一种机制。阐明这些机制将为开发 EC 的新型治疗干预提供途径。
