Researchers have discovered a previously unknown mechanism that promotes the growth and spread of cancer, in a new study.
According to a study by researchers at The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) and at Children's Hospital in Los Angeles, tiny vesicles released by tumour cells are taken up by healthy immune cells, causing the immune cells to discharge chemicals that foster cancer-cell growth and spread,
The study uses lung cancer cells to show that the vesicles contain potent regulatory molecules called microRNA, and that the uptake of these molecules by immune cells alters their behaviour.
The process in humans involves a fundamental receptor of the immune system called Toll-like receptor 8 (TLR8).
The findings suggest a new strategy for treating cancer and diseases of the immune system, the researchers say, and a new role for microRNA in the body.
"This study reveals a new function of microRNA, which we show binds to a protein receptor," Dr. Carlo Croce, principal investigator of the study, said.
"This tells us that some cancer-released microRNAs can bind and activate a receptor in a hormone-like fashion, and this has not been seen before," he said.
MicroRNAs help control the type and amount of proteins that cells make, and they typically do this by binding with the messenger-RNA that encodes a protein.
"In this study we discovered a completely new mechanism used by cancer to grow and spread, therefore we can develop new drugs that fight tumors by entering this newly identified breach in cancer's fortress," Dr. Muller Fabbri, co-corresponding author and first author of the study from the University of Southern California, said.
"Equally exciting, we show that this mechanism involves a fundamental receptor of the immune system, TLR8, suggesting that the implications of this discovery may extend to other diseases such as autoimmune and inflammatory diseases," Fabbri said.
Key findings of the study include - lung tumour cells secrete microRNA-21 and microRNA-29a in vesicles called exosomes, and these exosomes are taken up by immune cells called macrophages located where tumour tissue abuts normal tissue.
Secondly, in human macrophages, microRNA-29a and microRNA-21 bind with TLR8, causing the macrophages to secrete tumour-necrosis-factor alpha and interleukin-6, two cytokines that promote inflammation.
Finally, increased levels of the two cytokines were associated with an increase in the number of tumors per lung in an animal model, while a drop in those levels led to a drop in the number per lung, suggesting that they also play a role in metastasis.
The study has been published in the early edition of the Proceedings of the National Academy of Sciences.