Abstract:
Breast cancer is most common in women, and in most cases there is no evidence of spread and the primary tumor is removed, resulting in a \'cure\'. However, in 10% to 30% of these women, distant metastases recur after years to decades. This is due to breast cancer cells disseminating to distant organs and lying quiescent. This is called metastatic dormancy. Dormant cells are generally resistant to chemotherapy, hormone therapy and immunotherapy as they are non-cycling and receive survival signals from their microenvironment. In this state, they are clinically irrelevant. However, risk factors, including aging and inflammation can awaken dormant cells and cause breast cancer recurrences, which may happen even more than ten years after the primary tumor removal. How these breast cancer cells remain in dormancy is being unraveled. A key element appears to be the mesenchymal stem cells in the bone marrow that have been shown to promote breast cancer metastatic dormancy in recent studies. Indirect co-culture, direct co-culture and exosome extraction were conducted to investigate the modes of signal operation. Multiple signaling molecules act in this process including both protein factors and microRNAs. We integrate these studies to summarize current findings and gaps in the field and suggest future research directions for this field.
摘要:
乳腺癌在女性中最常见,在大多数情况下,没有扩散的证据,原发肿瘤被切除,导致“治愈”。然而,在10%到30%的女性中,远处转移在几年到几十年后复发。这是由于乳腺癌细胞扩散到远处的器官并处于静止状态。这称为转移性休眠。休眠细胞通常对化疗有抗性,激素治疗和免疫疗法,因为它们是非循环的,并从其微环境中接收生存信号。在这种状态下,它们在临床上无关紧要。然而,危险因素,包括衰老和炎症可以唤醒休眠细胞并导致乳腺癌复发,这可能发生在原发性肿瘤切除后的十年以上。这些乳腺癌细胞如何保持休眠正在被解开。一个关键因素似乎是骨髓中的间充质干细胞,在最近的研究中已显示出可促进乳腺癌转移休眠。间接共同文化,进行直接共培养和外泌体提取以研究信号操作模式。多种信号分子在此过程中起作用,包括蛋白质因子和microRNA。我们整合这些研究以总结该领域的最新发现和差距,并提出该领域的未来研究方向。