Extracellular vesicles in the biology of brain tumour stem cells – Implications for inter-cellular communication, therapy and biomarker development

 Extracellular vesicles (EVs) play a vital role in brain tumour stem cell (BTSC) biology by mediating inter-cellular communication within the tumour microenvironment. They transfer oncogenic proteins, RNAs, and signaling molecules, influencing tumour growth, therapy resistance, and metastasis. Understanding EVs offers new opportunities for developing targeted therapies and reliable biomarkers for early detection and monitoring of brain tumours.

Introduction:
Brain tumour stem cells (BTSCs) are a subpopulation within brain tumours, such as glioblastoma, that drive tumour initiation, progression, recurrence, and therapy resistance. Understanding the mechanisms that maintain BTSCs is crucial for developing more effective treatments.

Role of Extracellular Vesicles (EVs):
Extracellular vesicles — including exosomes and microvesicles — are nano-sized, membrane-bound particles secreted by cells to transport bioactive molecules like proteins, lipids, mRNAs, and microRNAs. In brain tumours, BTSCs release and receive EVs, which shape the tumour microenvironment and modulate cell behaviour.

Inter-cellular Communication:
EVs mediate communication between BTSCs and other tumour cells, endothelial cells, and immune cells. They promote angiogenesis, suppress anti-tumour immunity, and enhance invasion and metastasis by transferring oncogenic signals. This inter-cellular exchange contributes significantly to tumour heterogeneity and resistance to standard therapies.

Therapeutic Implications:
Targeting EV biogenesis, release, or uptake represents a promising strategy to disrupt malignant communication pathways in brain tumours. Moreover, EVs can be engineered as therapeutic delivery vehicles to transport drugs or genetic material selectively to tumour sites, potentially overcoming the blood–brain barrier.

Biomarker Development:
EVs circulating in blood or cerebrospinal fluid carry tumour-specific cargo that reflects the molecular status of BTSCs. Thus, they are emerging as non-invasive biomarkers for early diagnosis, prognosis, treatment monitoring, and minimal residual disease detection in brain tumour patients.

Key Roles in BTSC Biology:

  1. Stemness Maintenance: EVs from BTSCs can transfer stemness-promoting factors (e.g., SOX2, OCT4 mRNAs) to non-stem tumour cells, promoting dedifferentiation.

  2. Microenvironment Modulation: BTSC-derived EVs reprogram surrounding stromal and immune cells to create a pro-tumour niche. They can promote angiogenesis by delivering VEGF or pro-angiogenic miRNAs to endothelial cells.

  3. Therapy Resistance: EVs can carry drug-efflux transporters and anti-apoptotic signals. They also spread resistance traits to other tumour cells.

  4. Immune Evasion: EVs may suppress immune surveillance by delivering immunosuppressive molecules (e.g., PD-L1) or modulating microglia and T cells.

Therapeutic Opportunities:
Researchers are exploring strategies to block EV release (e.g., by targeting Rab GTPases involved in vesicle trafficking) or uptake. Another approach is to harness EVs as natural delivery systems — they can be engineered to carry siRNAs, chemotherapeutics, or CRISPR-Cas9 components to BTSCs, with better brain penetration than synthetic nanoparticles.


Potential as Biomarkers:
EVs can be isolated from cerebrospinal fluid (CSF) or blood. Their cargo — mutated EGFRvIII, IDH1, or specific miRNAs — can serve as biomarkers for diagnosis, prognosis, or treatment monitoring. Liquid biopsy using EVs offers a less invasive alternative to repeated brain biopsies.

Current Challenges and Future Directions:
Despite their promise, clinical translation faces hurdles:

  • Standardized isolation and characterization protocols are still evolving.

  • Distinguishing tumour-derived EVs from normal brain cell EVs in circulation remains challenging.

  • Large-scale trials are needed to validate EV-based biomarkers and therapies.

Conclusion
In sum, extracellular vesicles are key mediators of inter-cellular signalling in brain tumour stem cell biology, contributing to malignancy and treatment failure. Unlocking their mechanisms and therapeutic potential may revolutionize brain cancer diagnosis, monitoring, and treatment, offering hope for tackling these devastating diseases.


Comments

Post a Comment

Popular posts from this blog

Complexity

Image
1. General Definition Complexity describes systems, phenomena, or problems characterized by multiple interacting components, unpredictability, and often emergent behavior. These systems resist simplification and require holistic approaches to understanding and managing. 2. Characteristics of Complexity a. Interdependence The parts or elements within the system are interdependent, meaning the behavior of one part affects others. This interconnectedness often creates cascading effects. b. Emergence Complex systems display properties or behaviors that are not present in their individual components but emerge from their interactions. For instance, consciousness arises from neural interactions in the brain. c. Nonlinearity Outcomes are not proportional to inputs, and small changes in one part of the system can lead to disproportionate effects elsewhere (butterfly effect). This makes prediction difficult. d. Dynamism Complex systems are dynamic, constantly evolving due to interactions among ...
Read more
Image
 International Research Excellence Best Paper Awards Website link:  https://bestpaperawards.com/ # Social Sciences # Psychology #Arts # Psychology #Agriculture #Science
Read more

Research Training and Scholarly Activity during General Pediatric Residency in Canada

Image
                        Research training and scholarly activity are integral components of general pediatric residency programs in Canada. They ensure that residents are well-equipped with the skills needed to critically evaluate and conduct research, which in turn contributes to the advancement of pediatric healthcare. Here are some key points and aspects of this training: Structure of Research Training Research Curriculum : Many residency programs include a structured curriculum that covers essential topics such as research methodology, biostatistics, epidemiology, and ethics in research. Workshops and Seminars : Regular workshops and seminars on research design, data analysis, and scientific writing are commonly part of the training. Protected Research Time : Programs often provide protected time during the residency for residents to focus on their research projects, ensuring they can dedicate sufficient time to their schol...
Read more