Increased expression of CX43 on stromal cells promotes leukemia apoptosis

Shijie Yang; Qin Wen; Yao Liu; Cheng Zhang; Maihong Wang; Guo Chen; Yi Gong; Jiangjian Zhong; Xuelian Chen; Andres Stucky; Jiang F. Zhong; Xi Zhang

doi:10.18632/oncotarget.6249

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Research Papers:

Increased expression of CX43 on stromal cells promotes leukemia apoptosis

Shijie Yang, Qin Wen, Yao Liu, Cheng Zhang, Maihong Wang, Guo Chen, Yi Gong, Jiangjian Zhong, Xuelian Chen, Andres Stucky, Jiang F. Zhong _ and Xi Zhang

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Oncotarget. 2015; 6:44323-44331. https://doi.org/10.18632/oncotarget.6249

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Abstract

Shijie Yang1,2,*, Qin Wen1,2,*, Yao Liu1,2, Cheng Zhang1,2, Maihong Wang2, Guo Chen2, Yi Gong2, Jiangjian Zhong3, Xuelian Chen1, Andres Stucky1, Jiang F. Zhong1, Xi Zhang1,2

1Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA

2Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China

3Z-Genetic Medicine LLC, Temple City, CA, USA

*These authors have contributed equally to this work

Correspondence to:

Jiang Zhong, e-mail: [email protected]

Xi Zhang, e-mail: [email protected]

Keywords: leukemia, bone marrow stromal cells, apoptosis

Received: August 14, 2015 Accepted: October 14, 2015 Published: October 27, 2015

ABSTRACT

Connexin 43 (Cx43) induced apoptosis has been reported in solid tumors, but the effect of Cx43 expressed by bone marrow stromal cells (BMSC) in leukemia has not been fully investigated. Manipulating Cx43 expression could be a potential therapeutic strategy for leukemia. Here, we investigate the effect of Cx43 expressed by BMSCs (human Umbilical Cord Stem Cells over-expressed CX43, Cx43-hUCSC) on leukemia cells. When co-cultured with Cx43-hUCSC, leukemia cells show significant lower growth rate with increasing apoptosis activity, and more leukemia cells enter S phase. Functional assays of fluorescence recovery after photo bleaching (FRAP) showed improved gap junctional intercellular communication (GJIC) on leukemia cells when co-cultured with Cx43-hUCSC (p < 0.01). In a mouse minimal disease model, the mean survival time and mortality rate were significantly improved in mice transplanted with Cx43-hUCSC. Our results indicate that Cx43 expressed by BMSC induces apoptosis on leukemia cells. Small molecules or other pharmaceutical approaches for modulating Cx43 expression in BMSCs could be used for delaying relapse of leukemia.

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Research Papers:

Increased expression of CX43 on stromal cells promotes leukemia apoptosis

Abstract