Tumor-Derived Exosomes Containing GTPase Rab11a Can Drive Cancer Growth and Treatment Resistance, New Results from University of Oxford Suggest

Collaborative Cancer Research UK-funded studies from University of Oxford researchers have revealed a new mechanism by which cancer cells adapt to the stresses they encounter as they grow and respond to therapies. This mechanism involves cells releasing small vesicles, known as exosomes. These exosomes can contain complex mixtures of proteins, RNAs, and other molecules, which can reprogram surrounding cells. Exosomes are thought to be released by all cells in the body and play important roles in many processes in healthy individuals, such as immunity and reproduction. But, in cancer, they can sometimes drive pathological changes such as tumor growth and metastasis. Up until now, research has suggested that exosomes are made in compartments in cells, known as late endosomes, which are also used to keep cells healthy by clearing out damaged proteins and cell structures. By combining complementary analysis in fruit flies and human cancer cells, the collaborative teams have shown that exosomes are also made in the cell’s recycling system, which diverts reusable proteins away from the waste disposal system. They are called Rab11a-exosomes and carry a different set of cargos that may help cancers to grow and survive current treatments. As a tumor grows larger, the cells within it are starved of key nutrients such as amino acids, and these stressed cells produce Rab11a-exosomes loaded with molecules made by the cancer cells. According to Associate Professor Deborah Goberdhan (photo), who led the research, “These ‘bad exosomes’ can then give other cells around them a growth-promoting boost and can potentially lead to selection of more aggressive cell types and a worse outcome.
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