First ever study shows how astrocytes help to spread glioma.
A glioma is a type of tumour that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain. Gliomas make up about 30% of all brain and central nervous system tumours and 80% of all malignant brain tumours. The exact causes of gliomas are not known. High-grade gliomas are highly vascular tumors and have a tendency to infiltrate. They have extensive areas of necrosis and hypoxia. Often, tumour growth causes a breakdown of the blood–brain barrier in the vicinity of the tumor.
High-grade gliomas are fast-growing tumours. with a poor prognosis, especially for older patients. For patients with a Grade IV glioblastoma, the average survival time is approximately 12 months. Few patients with glioblastoma (Grade IV glioma) survive beyond three years with conventional treatment. Therefore, research has primarily concentrated on the mode of proliferation and stemming the spread of this cancer. Now, a new study from researchers at University of British Columbia suggests treatments should target the cells around a tumour to stop it from spreading. Two opensource studies have been published by the team in the journal Oncotarget.
Previous studies show that gap junctions are a specialized intercellular connection between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulated gate between cells. When found in nerves they are also referred to as an electrical synapse. Since gap junctions form by the docking of hemichannels from adjacent cells, three types of gap junctions can form during cancer progression, defined by the apposed cell types these are tumour-tumour, tumour-stroma, and stroma-stroma.
Gap junctions between tumour cells have been studied extensively during the past 50 years, and have mostly been demonstrated to act as tumour suppressors due to their positive effect on growth control. However, the team note that the role of gap junctions between tumour cells and stromal cells is less well characterized. Earlier studies suggest that they play an opposite role in cancer progression, in that, gap junctions between cancer cells and stromal cells seem to be critical for cancer cells to invade
The current study systematically examined the roles of three different kinds of gap junctions in glioma invasion (glioma-glioma, glioma-astrocyte, and astrocyte-astrocyte). The results show that glioma-glioma gap junctions suppress glioma invasion, while glioma-astrocyte and astrocyte-astrocyte gap junctions promote glioma invasion. Earlier studies show that astrocytes are a type of cell that regulate the environment in the brain to create favourable conditions for brain functions. Due to their connectivity with both stroma and the blood-brain-barrier the team decided astrocytes were an obvious culprit for glioma-gap junction spread.
Furthermore, the data findings show that the invasive effect of glioma-astrocyte and astrocyte-astrocyte gap junctions is enabled, at least in part, by the transfer of microRNA, specifically miR-5096, from glioma to astrocyte and that the effect may be amplified by signal spread among astrocytes. The lab explain that microRNAs are little pieces of genetic code that act as master switches, turning specific sets of genes on and off. The results highlight the complexity of the role of gap junctions in a tumour microenvironment and reveal for the first time that glioma cells modify stromal cells through transfer of microRNA.
The researchers state that these results reveal an alternative route to rein in the glioma cancer cells. They go on to add that to their knowledge this is the first evidence that microRNA can go from glioma cells into astrocytes and reprogram them to provide an altered environment that stimulates tumour growth and invasion.
For the future the lab surmise that a treatment should now be considered to temporarily modify healthy astrocytes around the tumour so the cancer cells can’t hijack them and spread any further.
Source: University of British Columbia