Up-regulation of Cx43 expression and GJIC function in acute leukemia bone marrow stromal cells post-chemotherapy.
Gap junction intercellular communication (GJIC) among bone marrow stromal cells (BMSCs) most frequently occurs through a channel composed of connexin43 (Cx43). Dysregulation of connexin expression is believed to have a role in carcinogenesis. In earlier work, we found that in acute leukemia BMSCs, expression of Cx43 and functioning GJIC declined. However, there has been no evaluation of whether GJIC in BMSCs in complete remission (CR) post-chemotherapy is different from GJIC pre-chemotherapy. We studied Cx43 expression and tested GJIC function in human bone marrow cultures under different physiological and pathological conditions. To assay Cx43 expression we used immunocytochemistry, laser scan confocal microscopy (LSCM), flow cytometry and RT-PCR. The results showed that the expression level of Cx43 and its mRNA in acute leukemia BMSCs post-chemotherapy was significantly higher and similar to normal levels than in primary acute leukemia BMSCs (p<0.01). Functional tests in cultures using dye transfer and fluorescence recovery after photobleaching (FRAP) assays showed that the function of GJIC in acute leukemia BMSCs was significantly improved following effective chemotherapy. Our findings suggest Cx43 and GJIC might be involved in the courses of occurrence, development and termination of acute leukemia, and effective chemotherapy could improve Cx43 expression and GJIC function that were dysfunctional prior to treatment.
Liu
Yao
Y
Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Shapingba District, Xinqiao Street, Chongqing 400037, China.
Zhang
Xi
X
Li
Zhong-jun
ZJ
Chen
Xing-hua
XH
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D018031:Connexin 43 / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D018031:Connexin 43; D012333:RNA, Messenger