Rutgers New Jersey Medical School, Department of Medicine, Newark, NJ, 07103, USA; Rutgers School of Graduate Studies at New Jersey Medical School, Newark, NJ, 07103, USA.
Rutgers New Jersey Medical School, Department of Medicine, Newark, NJ, 07103, USA.
Cancer Lett. 2020 Sep 28;488:9-17. doi: 10.1016/j.canlet.2020.05.026. Epub 2020 May 30.
Breast cancer (BC) remains a clinical challenge despite improved treatments and public awareness to ensure early diagnosis. A major issue is the ability of BC cells (BCCs) to survive as dormant cancer cells in the bone marrow (BM), resulting in the cancer surviving for decades with the potential to resurge as metastatic cancer. The experimental evidence indicates similarity between dormant BCCs and other stem cells, resulting in the preponderance of data to show dormant BCCs being cancer stem cells (CSCs). The BM niche and their secretome support BCC dormancy. Lacking in the literature is a comprehensive research to describe how the hypoxic environment within the BM may influence the behavior of BCCs. This information is relevant to understand the prognosis of BC in young and aged individuals whose oxygen levels differ in BM. This review discusses the changing information on vascularity in different regions of the BM and the impact on endogenous hematopoietic stem cells (HSCs). This review highlights the necessary information to provide insights on vascularity of different BM regions on the behavior of BCCs, in particular a dormant phase. For instance, how the transcription factor HIF1-α (hypoxia-inducible factor 1 alpha), functioning as first responder under hypoxic conditions, affects the expression of specific gene networks involved in energy metabolism, cell survival, tumor invasion and angiogenesis. This enables cell fate transition and facilitates tumor heterogeneity, which in turn favors tumor progression and resistance to anticancer treatments Thus, HIF1-α could be a potential target for cancer treatment. This review describes epigenetic mechanisms involved in hypoxic responses during cancer dormancy in the bone marrow. The varied hypoxic environment in the BM is relevant to understand the complex process of the aging bone marrow for insights on breast cancer outcome between the young and aged.
尽管治疗方法和公众意识的提高有助于早期诊断，但乳腺癌 (BC) 仍然是一个临床挑战。一个主要问题是 BC 细胞 (BCC) 作为休眠癌细胞在骨髓 (BM) 中存活的能力，导致癌症在几十年后仍有潜在的转移风险。实验证据表明休眠 BCC 与其他干细胞之间存在相似性，这导致大量数据表明休眠 BCC 是癌症干细胞 (CSC)。BM 生态位及其分泌组支持 BCC 休眠。文献中缺乏全面的研究来描述 BM 中的低氧环境如何影响 BCC 的行为。了解年轻和老年个体 BC 的预后与 BM 中的氧气水平有关，这方面的信息是相关的。这篇综述讨论了 BM 不同区域血管生成的变化信息及其对内源性造血干细胞 (HSC) 的影响。这篇综述强调了提供不同 BM 区域血管生成对 BCC 行为（特别是休眠期）的见解所需的必要信息。例如，转录因子 HIF1-α（缺氧诱导因子 1α）在缺氧条件下作为第一反应者的作用如何影响参与能量代谢、细胞存活、肿瘤侵袭和血管生成的特定基因网络的表达。这使细胞命运发生转变并促进肿瘤异质性，从而有利于肿瘤进展和对抗癌治疗的抵抗。因此，HIF1-α 可能是癌症治疗的潜在靶点。本综述描述了在骨髓中癌症休眠期间缺氧反应涉及的表观遗传机制。BM 中多样化的低氧环境对于了解衰老骨髓的复杂过程以了解年轻和老年个体之间乳腺癌的结果是相关的。
