SBI’s Exo-NGS Service drives discoveries and fuels insights into glioblastoma heterogeneity and, thus, pathogenicity.

Glioblastoma is the most common and highly aggressive primary brain cancer in adults. Invasiveness, intratumoral heterogeneity, and resistance to therapy are some of the hallmarks of the disease and are particularly apparent in subpopulations of glioblastoma stem-like cells (GSCs). In light of recent findings that extracellular vesicles (EVs) can alter the tumor micoenvironment, and that EVs mediate cell-cell communications, a group of researchers investigated the role of EVs, specifically EV miRNAs from GSCs, in GSC heterogeneity. The verdict? Godlewski, et al,1 found that not only do glioblastoma subpopulations show a diversity of EV miRNAs, EVs derived from one subpopulation of GSCs can reprogram miRNA expression when taken up by a different group of GSCs, suggesting that EVs can propagate heterogeneity in glioblastoma.

“EV-microRNA transfer between different subpopulations of tumor cells should be thus recognized as an important aspect of tumor intricacy that may propagate heterogeneity of GBM; thus, EV-microRNA secretion and uptake may be an additional trait of cellular adaptation into different anatomic niches.”1

The Challenges: With glioblastoma resistant to treatment, likely due to the presence of highly invasive and heterogenous subpopulations of GSCs, understanding the underlying drivers of GSC heterogeneity may provide new, more effective avenues to explore in the fight against this deadly disease.

The Current State: While EVs have been shown to affect the tumor microenvironment, their role in the pathogenesis of glioblastoma had not been previously examined.

The Advances: In their paper, “MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer,” Godlewski, et al,1 show that distinct subpopulations of patient-derived GSCs release distinguishably different and characteristic populations of EVs as determined by the EV miRNA content, and that these population-specific EVs can alter the invasiveness of other cell subpopulations. In addition to enhancing invasiveness, the GSC EVs alter global miRNA expression in the target cells, thus increasing tumor heterogeneity.

SBI Service Used: Godlewski, et al, 1 used SBI’s end-to-end Exo-NGS Service for anaylsis of EV miRNAs. With the ability to deliver powerful EV miRNA information from as little as 1 ng of total RNA, and an offering which includes full-service scientific support from sample preparation up to and including data analysis and interpretation, SBI’s Exo-NGS Service accelerates discovery and drives insight.

References

  1. Godlewski, et al. MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer. Stem Cell Reports. 2017 Jun 6; 8(6): 1497–1505. PMCID: PMC5470095.