Research Highlights
Conversion of Normal Cells to Pro-tumorigenic Lung Cancer Cells Can Occur by the Transfer of Micro RNAs From Circulating Extracellular Vesicles
Institution:
Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
Team:
Pontis F., Roz L., Mensah M., Segale M., Moro M., Bertolini G., Petraroia I., Centonze G., Ferretti A.M., Sautoni P., Pastorino U., Fortunato, O., and Sozzi, G.
Application:
In vitro interaction among extracellular vesicles to evaluate their pro-tumorigenic activity
Disease Model:
Lung Cancer
Hydrogel:
VitroGel® 3D
The use of biomarkers for the early detection of cancer is an active and ongoing field of study. In particular, the development of highly predictive non-invasive biomarkers would be a great boon for many cancer prevention programs. Lung cancer remains one of the leading causes of cancer-related mortality despite decades of progress. Recently, the potential of extracellular vehicles (EVs) as a biomarker has come to light, as they are becoming increasingly recognized for their central role in intercellular communication. EVs carry several types of “cargo” that can be delivered from one tissue to another. One such component carried by EVs is micro RNAs (miRNAs), which have been shown to be involved in tumorigenesis through their roles as either oncogenes or tumor suppressors. The research team in this study sought to assay the miRNAs released from EVs in cancer-free individuals who were at high risk for developing a certain type of cancer based on environmental or behavioral characteristics. They focused on lung cancer by isolating and studying EV-miRNAs from plasma samples from heavy smokers identified as high risk for lung cancer. The hope was that the pro-tumorigenic signals from EVs could be used as a powerful diagnostic tool.
Plasma samples from older (50–75-year-old) heavy smokers were collected at the Italian National Tumor Institute in Milan. Extracellular vesicles were isolated and examined both in vivo in a mouse environment and in vitro in tissue culture environment. Having previously identified suites of microRNAs that are potentially linked with lung cancer risk, the microRNA signature classifier (MSC), the investigators split the samples into two groups, one that contained high ratios of certain miRNAs (the MSCpos group) and one that contained low ratios (the MSCneg group). They then examined the in vitro interaction between EVs from both groups and different cells that would be found in the lung microenvironment, such as endothelial cells and fibroblasts. The cells were incubated with the EVs and seeded on the VitroGel 3D hydrogel system. The cell proliferation after 14 days was monitored and those from the MSCpos group were compared to those from the MSCneg group alongside a no treatment control. The results showed that EVs from the MSCpos group were significantly more likely to induce a tumorigenic phenotype in transformed bronchial epithelial cells than those from the MSCneg group (P = 0.0014). The oncoprotein c-Myc was implicated in the cancerous induction, as higher levels of this protein were observed in the MSCpos EVs than the MSCneg EVs. Two specific microRNAs, miR-126 and miR-320 were singled out as being associated with this conversion. Consequently, the team showed for the first time that different miRNAs carried in EVs released from healthy individuals with a high risk of lung cancer have a pro-tumorigenic role in the promotion of lung cancer.
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