EVs in Cancer
Overview
The mechanisms underlying cancer recurrence and progression, which hinder complete eradication of the disease, remain largely unknown and represent urgent issues to be addressed.
In recent years, extracellular vesicles (EVs), also known as exosomes, secreted by cancer cells have gained attention for their roles in cancer progression and metastasis. EVs are lipid bilayer-enclosed vesicles ranging from 50 to 200 nm in diameter, similar in size to viruses. They contain fragments of mRNA and DNA, various proteins, and microRNAs (miRNAs), and are secreted by most types of cells. After EVs are taken up by recipient cells, the enclosed miRNAs suppress the expression of specific genes, leading to phenotypic changes. Cancer cells may exploit EV-mediated cell-to-cell communication between different tissues to impair the microenvironment of distant organs, potentially facilitating metastasis.
In our previous studies, we have identified several cancer-specific miRNAs in tumor-derived EVs and narrowed down promising candidates for prognostic biomarkers.
Research Focus
This study aims to address the following three goals:
- Validation of miRNAs as prognostic markers for cancer and development of diagnostic kits.
- Identification of miRNAs specifically enriched in EVs from non-recurrence cancer patients and their application to nucleic acid therapeutics.
- Elucidation of the mechanisms by which EVs and their miRNAs contribute to cancer metastasis.
Research Strategy
- Candidate miRNAs will be validated using qPCR not only in serum-derived EVs but also in urine-derived EVs. Diagnostic performance will be evaluated using ROC curve analysis.
- Comprehensive gene expression profiling will be used to compare EV-contained miRNAs between recurrence and non-recurrence cancer patient groups to identify non-recurrence-specific miRNAs.
- We have already established cancer cell lines that stably produce EVs containing both luciferase and red fluorescent protein mCherry. These cells will be transplanted into mice, and in vivo imaging will be used to track EV uptake and identify the recipient tissues during the metastatic process. Furthermore, by applying anti-miRNA–based knockdown strategies, we will generate fluorescent and luminescent exosomes selectively lacking individual miRNAs, aiming to identify those most strongly associated with cancer metastasis. We aim to pinpoint metastasis-associated miRNAs and explore their application in nucleic acid-based therapies.
Link to Research Seeds Collection (Japanese)