Mohd Ali Norlaily, Yeap Swee Keong, Ho Wan Yong, Boo Lily, Ky Huynh, Satharasinghe Dilan Amila, Tan Sheau Wei, Cheong Soon Keng, Huang Hsien Da, Lan Kuan Chun, Chiew Men Yee, Ong Han Kiat
Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia.
Marine Biotechnology, China-ASEAN College of Marine Sciences, Xiamen University Malaysia Campus, Jalan Sunsuria, Bandar Sunsuria, Sepang, Selangor 43900, Malaysia.
Pharmaceuticals (Basel). 2020 Dec 24;14(1):8. doi: 10.3390/ph14010008.
Globally, breast cancer is the most frequently diagnosed cancer in women, and it remains a substantial clinical challenge due to cancer relapse. The presence of a subpopulation of dormant breast cancer cells that survived chemotherapy and metastasized to distant organs may contribute to relapse. Tumor microenvironment (TME) plays a significant role as a niche in inducing cancer cells into dormancy as well as involves in the reversible epithelial-to-mesenchymal transition (EMT) into aggressive phenotype responsible for cancer-related mortality in patients. Mesenchymal stem cells (MSCs) are known to migrate to TME and interact with cancer cells via secretion of exosome- containing biomolecules, microRNA. Understanding of interaction between MSCs and cancer cells via exosomal miRNAs is important in determining the therapeutic role of MSC in treating breast cancer cells and relapse. In this study, exosomes were harvested from a medium of indirect co-culture of MCF7-luminal and MDA-MB-231-basal breast cancer cells (BCCs) subtypes with adipose MSCs. The interaction resulted in different exosomal miRNAs profiles that modulate essential signaling pathways and cell cycle arrest into dormancy via inhibition of metastasis and epithelial-to-mesenchymal transition (EMT). Overall, breast cancer cells displayed a change towards a more dormant-epithelial phenotype associated with lower rates of metastasis and higher chemoresistance. The study highlights the crucial roles of adipose MSCs in inducing dormancy and identifying miRNAs-dormancy related markers that could be used to identify the metastatic pattern, predict relapses in cancer patients and to be potential candidate targets for new targeted therapy.
在全球范围内，乳腺癌是女性中最常被诊断出的癌症，并且由于癌症复发，它仍然是一个重大的临床挑战。存在一群休眠的乳腺癌细胞，它们在化疗后存活并转移到远处器官，这可能导致复发。肿瘤微环境（TME）作为一个生态位，在诱导癌细胞进入休眠状态方面发挥着重要作用，并且还参与了上皮-间质转化（EMT）的可逆过程，这种转化会导致患者出现与癌症相关的死亡的侵袭性表型。已知间充质干细胞（MSCs）会迁移到TME，并通过分泌含有外泌体的生物分子——微小RNA（microRNA）与癌细胞相互作用。了解MSCs与癌细胞通过外泌体微小RNA的相互作用，对于确定MSCs在治疗乳腺癌细胞和复发中的治疗作用非常重要。在本研究中，从MCF7-管腔型和MDA-MB-231-基底型乳腺癌细胞（BCCs）亚型与脂肪间充质干细胞间接共培养的培养基中收获外泌体。这种相互作用导致了不同的外泌体微小RNA谱，这些谱通过抑制转移和上皮-间质转化（EMT）来调节关键信号通路并使细胞周期停滞进入休眠状态。总体而言，乳腺癌细胞表现出向更具休眠性的上皮表型转变，这与较低的转移率和较高的化疗耐药性相关。该研究强调了脂肪间充质干细胞在诱导休眠以及识别与休眠相关的微小RNA标记物方面的关键作用，这些标记物可用于识别转移模式、预测癌症患者的复发情况，并成为新的靶向治疗的潜在候选靶点。
