Zhao Pan, Chen Yafang, Yue Zhijie, Yuan Ying, Wang Xiaofang
Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Leuk Res. 2017 Jun;57:20-26. doi: 10.1016/j.leukres.2017.02.005. Epub 2017 Feb 24.
Bone marrow mesenchymal stem cells (BM-MSCs) are key components of bone marrow microenvironment. Although the importances of BM-MSCs activation in myeloma cells growth, development, progression, angiogenesis are well known, their role in the regulation of myeloma stemness is unclear. In this study, myeloma cell lines (LP-1, U266) were co-cultured with BM-MSCs, we found that BM-MSCs could up-regulate the expression of key stemness genes and proteins (OCT4, SOX2, NANOG) and increase clonogenicity. Similarly, the mechanisms underlying the BM-MSC activation of myeloma stemness remain unclear. Here, we found that PCI-32765, a Bruton tyrosine kinase (BTK) inhibitor, treatment significantly down- regulate expression of key stemness genes and proteins in vitro co-culture system. Together, our results revealed that BM-MSCs could increase myeloma stemness via activation of the BTK signal pathway.
骨髓间充质干细胞（BM-MSCs）是骨髓微环境的关键组成部分。尽管BM-MSCs激活在骨髓瘤细胞生长、发育、进展、血管生成中的重要性已广为人知，但其在骨髓瘤干性调节中的作用尚不清楚。在本研究中，将骨髓瘤细胞系（LP-1、U266）与BM-MSCs共培养，我们发现BM-MSCs可上调关键干性基因和蛋白（OCT4、SOX2、NANOG）的表达并增加克隆形成能力。同样，BM-MSCs激活骨髓瘤干性的潜在机制仍不清楚。在此，我们发现布鲁顿酪氨酸激酶（BTK）抑制剂PCI-32765在体外共培养系统中处理可显著下调关键干性基因和蛋白的表达。总之，我们的结果表明BM-MSCs可通过激活BTK信号通路增加骨髓瘤干性。
