All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction

Journal of Hematology & Oncology

Jiang-fan Zhong¹  Xi Zhang²  Xing-hua Chen²  Kai Wan²  Xi-xi Xiang²  Jia-li Li²  Cheng Zhang²  Li Gao²  Lei Gao²  Shi-jie Yang²  Xue-lian Chen¹  Qin Wen²  Yao Liu¹ 

[1] Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles 90033, CA, USA;Department of Hematology, Xinqiao Hospital, the Third Military Medical University, Xinqiao Street, Chongqing 400037, China

关键词: Leukemia BMSCs;    Gap junctional intercellular communication;    Connexin 43;    Bone marrow stromal cells;    All-trans retinoic acid;   

Others  :  1232042
DOI  :  10.1186/s13045-015-0212-7

 received in 2015-07-01, accepted in 2015-09-28,  发布年份 2015

【 摘 要 】

Background

Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined.

Methods

Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP).

Results

ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment.

Conclusions

ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.

【 授权许可】

   
2015 Liu et al.

【 图 表 】

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