New research from The University of Texas MD Anderson Cancer Center (TX, USA) suggests that cancer exosomes can produce miRNAs that aid tumor growth via the assistance of the protein Dicer. The results also suggest that Dicer may be used as a biomarker for breast cancer and could lead to new research directions in diagnosis and treatment. The findings were published recently in the journal Cancer Cell.
Exosomes are small vesicles consisting of DNA, RNA and proteins enclosed in lipid bilayers, and are known to perform specialized functions such as coagulation and intercellular signaling. As they commonly form a source of disease-specific nucleic acids and proteins in bodily fluids, they are increasingly being studied for their potential as both indicators of disease and novel treatment approaches.
The role of miRNAs associated with exosomes in cancer progression is currently largely unknown. Several studies have suggested that miRNAs are present in exosomes and have speculated on their function in cancer.
However, a team of researchers from the MD Anderson Cancer Center, led by Raghu Kalluri , have demonstrated that exosomes released by cancer cells bioengineer miRNA molecules with the help of the protein Dicer, resulting in tumor growth.
Kalluri commented: “Exosomes derived from cells and blood serum of patients with breast cancer, have been shown to initiate tumor growth in non-tumor-forming cells when Dicer and other proteins associated with the development of miRNAs are present.”
“We demonstrated that inhibiting the action of Dicer in cancer exosomes significantly impairs tumor growth, raising the possibility that miRNAs in exosomes contributes to cancer progression.”
The MD Anderson study suggests that Dicer acts on its ‘host’ exosome to manipulate the surrounding cancer cells, thus creating an ‘oncogenic field effect’ and encouraging tumorigenesis.
Kalluri’s team demonstrated that breast cancer-associated exosomes contain specific miRNAs associated with a multiprotein complex known as RNA-induced silencing complex. In addition, the findings revealed that breast cancer exosomes also contain Dicer and two other proteins, namely AGO2 and TRBP, all of which encourage tumor growth.
Kalluri continued: “These studies reflect the need to evaluate the functional contribution of miRNA machinery in exosomes and their role in tumor progression and metastasis.”
A complete understanding of the interplay between Dicer and miRNA could widely benefit the understanding of breast cancer growth and metastasis. In the meantime, the findings provide an important platform for future research and could lead to the novel development of exosome-based biomarkers.