期刊
FASEB JOURNAL
卷 25, 期 1, 页码 255-264出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.10-155291
关键词
aggregation; 3D; spheroid; gap junction
资金
- Brown University
- Rhode Island Research Alliance
- National Institutes of Health (NIH) [RO1EB008664-01A1t, AR46798]
- Welch Foundation [AQ-1507]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [P01AR046798] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB008664] Funding Source: NIH RePORTER
Microtissue self-assembly is thought to be driven primarily by cadherins, while connexons have been examined mainly in intercellular coupling. We investigated whether connexon 43 (Cx43)-mediated cell adhesion modulates self-assembly of human KGN granulosa cells, normal human fibroblasts (NHFs), and MCF-7 breast cancer cells seeded into nonadhesive agarose gels. We found that treatment with anti-Cx43 E2 (112 mu g/ml), which suppresses Cx43 docking, significantly inhibited the kinetics of KGN and NHF self-assembly compared to the preimmune sera control (41.1 +/- 4.5 and 24.5 +/- 10.4% at 8 h, respectively). Likewise, gap junction inhibitor carbenoxolone also inhibited self-assembly of KGN, NHF, and MCF-7 cells in a dose-dependent manner that was specific to cell type. In contrast, Gap26 connexin mimetic peptide, which inhibits channel permeability but not docking, accelerated self-assembly of KGN and NHF microtissues. Experiments using selective enzymatic digestion of cell adhesion molecules and neutralizing N-cadherin antibodies further showed that self-assembly was comparably disrupted by inhibiting connexin-and cadherin-mediated adhesion. These findings demonstrate that connexon-mediated cell adhesion and intercellular communication differentially influence microtissue self-assembly, and that their contributions are comparable to those of cadherins.-Bao, B., Jiang, J., Yanase, T., Nishi, Y., Morgan, J. R. Connexon-mediated cell adhesion drives microtissue self-assembly. FASEB J. 25, 255-264 (2011). www.fasebj.org
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