MedicalResearch.com Interview with:
Natalie Artzi PhD
principal research scientist
MIT’s Institute for Medical Engineering and Science and
Assistant professor of medicine
Brigham and Women’s Hospital
Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Noam Shomron
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Metastases are the primary cause for mortality in breast cancer, the most common cancer in women regardless of ethnicity. Recent studies show that germline sequence variants, such as single-nucleotide polymorphisms (SNPs) in miRNA-binding sites, can disrupt the downregulation by miRNAs, with a profound effect on gene expression levels and consequentially on the phenotype, including increased risk for cancer.
In the current study, we aimed to determine the potential effect of SNPs within miRNA-binding sites on metastatic breast cancer progression and their potential use as suppression targets to prevent metastasis.
Our collaborators at Tel-Aviv Universityin a research led by Dr. Noam Shomron found that the SNP, rs1071738, located in a target site for miR-96 and miR-182 on the 3’-UTR of the PALLD gene, encodes the Palladin actin-associated protein, which is a documented player in breast cancer motility. In vitro experiments revealed a functional downregulation of Palladin levels by miR-96 and miR-182, which subsequently reduces migration and invasion abilities of breast cancer cells.
My lab then showed in an in vivo experiment that the use of nanoparticles embedded in a hydrogel scaffold as a miRNA delivery vehicle enables an efficient and specific delivery of miR-96/miR-182 directly to breast tumours, which results in marked reduction of breast cancer metastasis. We then proceeded to study the effect of combination therapy in which we will use a chemotherapy drug to shrink the primary tumor and the miRNAs to prevent metastasis. The intercalation of a chemotherapy drug, cisplatin, to the miR-conjugated nanoparticles further improved the effect, leading to significant reduction in both primary tumour growth and metastasis.
Our study highlights the therapeutic potential of miRNAs, and specifically miR-96 and miR-182, and support the importance of Palladin regulation in breast cancer metastasis.
MedicalResearch.com: What should readers take away from your report?
Response: This study introduces the therapeutic potential of miRNAs in breast cancer metastasis prevention. The delivery vehicle that was developed facilitates efficient, local and sustained release of miRNAs, as well as combined therapy of miRNAs with a chemotherapy drug. Our proposed treatment could potentially be administered to breast cancer patients shortly after malignant disease is confirmed, before surgical intervention, and could assist in reducing distal metastasis. In addition, the treatment can be applied locally as a washout procedure following resection to eliminate remaining malignant cells that may cause tumour recurrence and metastasis
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We are going to study the processes by which these specific miRNAs prevent metastasis and examine whether they can be used to treat cells that have already migrated to the blood stream before and dissemination at distant sites. We will further study the impact of administration mode and delivery vehicle design on metastasis prevention.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Natalie Artzi, Noam Shomron. Local microRNA delivery targets Palladin and prevents metastatic breast cancer. Nature Communications, 2016; 7: 12868 DOI: 10.1038/ncomms12868
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