Connexin 43 reduces spreading of gliomas
José Pichel Andrés/DICYT A study conducted by the Instituto de Neurociencias de Castilla y León (Incyl), an institute of neurosciences at the Universidad de Salamanca (Spain), has proved the increased expression of a protein called connexin 43 contributes to reduce an oncogene (a gene turning a normal cell into a tumor cell). In this case, we refer to the oncogene c-Src in glioma stem cells, the most common brain tumor. Consequently, the study suggests that connexin 43 may be useful to develop new therapies against brain tumors.
The researcher Ester Gangoso is one of the persons responsible of this research area, recently portrayed in an article in Glia. “We have worked with glioma cell lines to decrease their proliferation”, as DiCYT was told by her before giving a research seminar on this topic at Incyl.
Specifically, the main purpose of this team, led by José María Medina and Arantxa Tabernero, focuses on glioma stem cells, “the most resistant cells in current chemotherapies and radiation treatments”. For the time being, “we have managed to reduce the proliferation of these cells by increasing expression levels of connexin 43, a very important protein in the communication of astrocytes (cells at the central nervous system)”, the researcher explains.
Scientists have managed to describe that increased expression of connexin 43 decreases the ongogene’s activity and this “produces a cascade of signals decreasing transcription factors in stem cells” and, in turn, cell proliferation. Therefore, they may be working with a potential therapeutic target, because stimulation of this protein may inhibit tumor process.
One feature of gliomas is the inexistent communication among glial cells or astrocytes and connexin 43 increases these cells communication and, apparently, this is the way it prevents the oncogene’s activation. Actually, “the more malignant a tumor is, the lower is connexin 43 expression”, Ester Gangoso explains.
The researchers have conducted experiments consisting in the introduction of connexin 43 in glioma stem cells resulting in a declining of their proliferation. Although this is an in vitro study, in vivo studies have been conducted with mice during a stay of the researcher in a Parisian laboratory. “By causing neuronal damages in mice, astrocytes act and produce changes in some proteins, including connexin 43. When brain injuries are produced, astrocytes decrease this molecule and we found an increase in oncogene levels. All in all, the same happens in cell cultures.”
At this point, the end goal is to maintain experiments with stem cells and to “study if we are able to eliminate them, an experiment that would be the final touch for this work”. Furthermore, and taking into account the part of connexin 43 actually involved, they would like to study peptides that seem to produce the same results.
|Gangoso E, Ezan P, Valle-Casuso JC, Herrero-González S, Koulakoff A, Medina JM, Giaume C, Tabernero A. Reduced connexin43 expression correlates with c-Src activation, proliferation, and glucose uptake in reactive astrocytes after an excitotoxic insult. Glia. 2012 Dec;60(12):2040-9. doi: 10.1002/glia.22418.|