Exosome Research in Human Neuroblastoma
Neuroblastoma (NB) is an aggressive pediatric extracranial solid tumor that occurs in the developing sympathetic nervous system and exhibits unique clinical and prognostic features. High-risk NB (HR-NB is characterized by aggressive metastasis, high resistance to therapy, and fatal recurrence. Despite aggressive treatment, survival of HR-NB patients remains low.
Exosomes are nano-sized extracellular vesicles derived from the endocytosis pathway. Tumor-derived exosomes have been shown in multiple model systems to carry molecules that promote cancer progression. NB-derived exosomes have been shown to contain tumor-specific features, have higher DNA content compared to exosomes isolated from stromal cells, and may contribute to cancer cell progression, migration, and survival. Therefore, it is essential to understand the contribution of exosomes from the NB or tumor microenvironment (TME) to the biology of the disease.
Figure 1. The general characteristics of exosomes derived from NB tumor cells. (Jahangiri L, Ishola T., 2022)
The Role of Exosomes in NB Progression
Understanding the contribution of exosomes to NB progression enables a better understanding of its role in aggressive NB. In NB MYCN amplification is associated with poor patient prognosis. Research has found that exosomes produced by MYCN-amplified NB cells have different molecular content and contain essential metastable information compared to non-MYCN-amplified NB cells. This is essential for outlining how intercellular communication alters the invasiveness of cancer cells. In addition, exosomes play essential roles in critical cellular processes, including transcription factor occupancy and transcription elongation. NB-derived exosomes can also promote tumor growth and progression by affecting immune cells within the TME.
Figure 2. Mechanisms of exosome effects on the growth and spread of NB tumors. (Benito-Martín A, et al., 2023)
Exosomes as NB Biomarkers and Diagnostic Tools
Recently, there has been a growing interest in liquid biopsies. Liquid biopsy is a minimally invasive and easily accessible method that can provide complementary or even additional information to tissue biopsy. The release of exosomes is regulated by specific stimuli and its contents reflect the producing cells. Exosomes are stable in the circulation and protect the cargo from degradation. Therefore, accurate information about the characteristics of primary tumors can be obtained from exosomes. In this context, researchers used exosomal microRNA (exo-miRNA) as a circulating biomarker of response to chemotherapy. The exo-miRNA in plasma samples collected from HR-NB provides an index of chemoresistance that can be used for prognostic evaluation.
Figure 3. Diagnostic value of exosomes for NB patients for MYCN amplification status determination. (Jahangiri L, Ishola T., 2022)
Exosome-based NB Therapeutic Options
- Induction of Differentiation
Research has shown that HSP27 has an essential role in regulating NB differentiation. Researchers exposed the SH-SY5Y cell line to exosome-loaded siRNA targeting HSP27. Characterization of exosomes by electron microscopy and the presence of CD63 while monitoring exosome entry into the cells. Then, assessment of cell viability and screening for NB differentiation using neuromarkers. Results indicate that exosome-based delivery of therapeutic molecules is feasible and that induction of HSP27 expression promotes NB differentiation.
- Immunotherapy
Several studies have described how NB interacts with natural killer (NK) cells at the exosomal level and influences therapy. One research showed that miR-186-containing exosomes secreted by IL-15-activated NK cells induced cytotoxicity in MYCN-amplified NB cells. Targeted delivery of miR-186 reversed TGF-β-induced NK cell inactivation and immune escape and consistently reduced NB cell survival and migration.
| Cat No. | Product Name | Source |
| Exo-IC06 | HQExo™ Exosome-NK | Exosome derived from human NK cell line |
| Explore All Exosomes Isolated from Human NK Cell Line | ||
Understanding NB biology, diagnostic biomarkers, and therapeutic options is essential to resist NB. In recent years, exosomes have been one such promising research direction. Creative Biostructure, as a leader in exosome research, has a comprehensive range of exosome services, including exosome isolation, characterization, labeling, tracking, targeting, and functional analysis.
In addition, we provide a series of high-quality exosome products to help clients develop new strategies for NB therapy.
| Cat No. | Product Name | Source |
| Exo-CH14 | HQExo™ Exosome-SK-N-SH | Exosome derived from human neuroblastoma (SK-N-SH cell line) |
| Explore All Exosomes Isolated from Human Neuroblastoma | ||
Creative Biostructure specializes in exosome research, we provide exosome one-stop service and globally deliverable exosome products, please feel free to contact us for a formal quote.
References
- Jahangiri L, Ishola T. Exosomes in Neuroblastoma Biology, Diagnosis, and Treatment. Life (Basel). 2022. 12(11): 1714.
- Marimpietri D, et al. The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma. Int J Mol Sci. 2021. 22(8): 3964.
- Neviani P, et al. Natural Killer-Derived Exosomal miR-186 Inhibits Neuroblastoma Growth and Immune Escape Mechanisms. Cancer Res. 2019. 79(6): 1151-1164.
