间质细胞
淋巴瘤
克隆形成试验
癌症研究
骨髓
弥漫性大B细胞淋巴瘤
细胞培养
B细胞
生物
分子生物学
化学
免疫学
抗体
遗传学
作者
Zhiyun Lin,Bobin Chen,Ting Wu,Xiaoping Xu
出处
期刊:Acta Haematologica
[S. Karger AG]
日期:2018-01-01
卷期号:139 (4): 201-216
被引量:5
摘要
<b><i>Background/Aims:</i></b> Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. <b><i>Methods:</i></b> We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. <b><i>Results:</i></b> Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. <b><i>Conclusion:</i></b> Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells.
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