Carcinogenesis Advance Access published online on December 4, 2003
Carcinogenesis, doi:10.1093/carcin/bgh036
© 2003 by Oxford University Press
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CANCER BIOLOGY
1 Department of Cell Biology, Beijing Institute for Cancer Research, Peking University School of Oncology, Beijing 100034, P. R. China
* Corresponding author. E-mail: zqzhang{at}public3.bta.net.cn.
Received 4 February 2003
; revised 12 November 2003
; accepted 17 November 2003
The dysfunction of homologous and/or heterologous gap junctional intercellular communication (GJIC) has been implicated in tumorigenesis of many kinds of cells. Here, we characterized GJIC and the expression of connexins in six human lung carcinoma cell lines and lung fibroblasts (HLF). Compared with HLF, all the carcinoma cells showed reduced or little homologous GJIC. They expressed remarkably reduced Cx43 mRNA and Cx45 mRNA at different levels, but neither the Cx43 nor Cx45 proteins could be detected. However, using a preloading assay, transfer of calcein was observed between donor HLF cells and first order neighboring recipient tumor cells (recipient cells in 1000 fold excess). Transfer from tumor to HLF cells under the same conditions was not seen, although increasing the ratio of donor tumor cells to recipient HLF cells, and plating the cells at low density, did reveal weak transfer from tumor cells to HLF. Transfection of Cx43 into giant cell carcinoma PG cells increased homologous communication and eliminated the rectifying behavior of heterologous communication. This indicates that the apparent rectification of dye transfer between normal and tumor cells was a product of low rates of heterologous transfer linked to (1) rapid dilution of the dye to below detectable limits through a very well coupled cell population (tumor to HLF); and (2) concentration of dye in immediate neighbors in a poorly coupled cell population (HLF to tumor cells). These results suggest that the coupling levels may need to exceed a certain threshold to allow propagation of signals over a sufficient distance to affect behavior of a cell population. We propose that the relative rates of heterologous and homologous coupling of cell populations, and the "pool size" of shared metabolites in tumor cells and the surrounding normal tissue, are likely to be very important in the regulation of their growth.
gap junction, asymmetric coupling, connexin, lung carcinoma, lung fibroblasts
Effective asymmetry in gap junctional intercellular communication between populations of human normal lung fibroblasts and lung carcinoma cells
2 Department of Anatomy & Cell Biology, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada
3 Department of Biological Sciences, State University of New York at Buffalo, NY14260, USA
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