A novel and pivotal study on micro-RNA and cancer progression entitled “Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis” was published on Cancer Cell by Dr. Sonia A. Melo, part of Dr. Raghu Kalluri’s group from the Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston.
In this study, the research team found that exosomes, lipid bilayer protected vesicles with a nanoscale size of 50–140 nm that contain proteins, mRNA, and microRNAs (miRNAs), were associated with breast cancer cells and contained specific miRNAs associated with a complex of various proteins known as RNA-induced silencing complex (RISC). This group of proteins includes Dicer, AGO2 and TRBP, and together form a miRNA machinery that has the capacity to induce tumor growth.
Exosomes perform specific biological functions like coagulation, intercellular signaling and cell “waste management.” There has been an increased interest in exosomes since these molecules have been associated as possible biomarkers of disease and can open doors into new ways of treatment.
miRNAs are small functional RNA molecules that are not translated into proteins, i.e. non-coding RNAs, with a length of 18–24 nucleotides. These molecules control gene expression after transcription and play a crucial part in regulating several different pathways.
Kalluri’s team showed that exosomes secreted by breast cancer cells have a specific ability for miRNA biogenesis in a cell-independent way, contrary to what is observed in the exosomes released by normal cells. They also found that exosomes collected from cancer cells and serum from breast cancer patients, contained the RISC loading complex proteins, which are crucial in processing pre-miRNAs into mature miRNAs. The exosomes derived from cancer cells had the ability to change all the RNA molecules of target cells in a Dicer-dependent manner, transforming normal epithelial cells into tumor cells.
Furthermore, this study identified a mechanism by which cancer cells manipulate the surrounding cells and may induce cancer progression. The crosstalk between Dicer and its “host” exosome in cancers cells seems to induce a so-called “oncogenic field” effect in the neighbouring cells.
Importantly, the researchers suggest that the presence of Dicer in exosomes may be used as biomarker for the clinical detection of cancer.
“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,” said Raghu Kalluri, M.D., Ph.D., chair of the department of cancer biology at MD Anderson, in an MD Anderson press release. “These findings offer opportunities for the development of exosomes-based biomarkers and shed insight into the mechanisms of how cancer spreads.”
“The role of miRNAs associated with exosomes in cancer progression is largely unknown. Many studies have suggested the presence of miRNAs in exosomes and speculated on their function,” added Dr. Kalluri. “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.”
“These studies reflect the need to evaluate the functional contribution of miRNA machinery in exosomes and their role in tumor progression and metastasis,” he concluded.