Tumour cells send different types of messages from one cell to another aka people post letters, postcards, and parcels to their families, friends, colleagues or business. Cells can direct their messages using free moving proteins – postcards. They can wrap it in microvesicles with different cargo. Big microvesicles can take up big messages – parcels, small microvesicles or exosomes contain a limited number of texts – letters.
Tumour cells change their behaviour quickly adapting to anticancer therapies, so the messages they are sending. These messages can easily join blood stream and be read by researchers to understand how treatment is working and tumour cells are feeling. Reading these messages from blood is more favourable as blood tests are done on the regular bases during and after the treatment.
In our lab we investigate how neuroblasts communicate with each other and the entire body through exosomes. We are interested to see what they write in their letters – exosomes. Do drug resistant and sensitive neuroblasts write different texts? What is the difference and how we can use this difference to predict child response to anticancer therapy?
In one set of experiments, we found that exosomes from drug resistant neuroblasts stimulate growth of sensitive cells. The more resistant neuroblasts send more powerful messages pushing cells to grow faster.
In the other set of experiments, we partially cracked the message showing that their texts are different. This finding explains why more resistant neuroblasts send more growth stimulating messages.
All these findings will be presented at the upcoming conference Goodbye Flat Biology: Models, Mechanisms and Microenvironment in Berlin.
Schematic of exosome biogenesis and secretion. Cells produce exosomes through different pathways. This process is tightly regulated and controlled by numerous molecules. It can be triggered by many factors including extracellular stimuli (e.g., microbial attack, UV, drugs) and other stresses. The exosomes wrap up biologically active components such as proteins, RNA and miRNA. Exosomes can interact with recipient cells using four mechanisms: ligand/receptor interaction, protein transfer, membrane fusion or internalisation. Once exosomes entered the recipient cell, they release their content and re-programme the cell functions.
Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M. A comprehensive overview of exosomes as drug delivery vehicles – Endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta – Rev Cancer. 2014;1846(1):75–87.
El Andaloussi S, Mäger I, Breakefield XO, Wood MJ a, Andaloussi S EL, Mäger I, et al. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–57.
The schematic of exosomes was adapted from here