title: Increased expression of CX43 on stromal cells promotes leukemia apoptosis.
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.
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Yang
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Maihong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Z-Genetic Medicine LLC, Temple City, CA, USA.
authors.forename: Jiangjian
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Stucky
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jiang F
authors.initials: JF
authors.lastname: Zhong
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Hematology and Blood Transfusion, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D036101:Cord Blood Stem Cell Transplantation; D004789:Enzyme Activation; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019899:Paracrine Communication; D012008:Recurrence; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D020169:Caspases
keywords: apoptosis; bone marrow stromal cells; leukemia