Understanding why a tumor metastasizes in specific organs and do not in others is one of the top goals of oncology, and also one of the oldest.
Researchers have collected evidence that tumors release millions of vesicles carrying representative samples of their proteins and genetic content. These are called exosomes and, like 'messenger vessels' or 'scouts', they are in charge of ensuring that the recipient organs are prepared to host the tumor cells. Specifically, the exosomes trigger the necessary molecular response -- inflammation, vascularization, etc. -- in the recipient organ to welcome the tumor cells, so that when they arrive they can proliferate.
The authors selected 20 tumor cell lines from around ten different tumors, in which it is known that some metastasize to specific target organs; the lungs, liver, brain or bones. They analyzed the proteins in their exosomes, nearly a thousand proteins, searching for those that could fulfil the role of a zip code.
They focused on a family of proteins called integrins, because these are present on the membrane of the exosomes where, theoretically, the destination 'label' should be found. This proved to be a sound strategy. From among a thousand proteins, they found that there were indeed specific combinations of integrins associated with metastasis to the lungs, and with metastasis to the liver
If a tumor is 'tricked', by changing the destination code, it will colonize the organ that is specified. This has been tested with tumor cells that normally would go to the bones and, following the intervention of the researchers, went to the lungs. These data support that the 'soil' is as important as the 'seed' in the metastatic process.
Additional proof of the importance of integrins in metastatic nesting is that, as the study shows, when specific integrins are blocked in tumors that metastasize to specific organs -- for example breast cancer to lungs and pancreas cancer to the liver -- metastasis is reduced in these organs.
The researchers have also discovered the molecular signals that intercede in the reaction of the recipient tissue when the exosomes arrive. Specifically, these signals involve an increase in genes of the S100 family, which is known for provoking inflammatory signals; inflammation is a process associated with cancer.