Scientists at Massachusetts General Hospital and the Massachusetts Institute of Technology (MIT) have possibly discovered what allows tumors to spread and grow — otherwise known as metastasis — all with the use of nanotechnology and microscopy. Their results, which were published in the scientific journal Nature Communications on Dec. 15, might pave the way for disrupting this process by using drugs to beef up the resistance of endothelial cells, or cells that line the walls of blood vessels.
"Endothelial cells line every blood vessel and are the first cells in contact with any blood-borne element," said Elazar Edelman, one of the leading scientists on the team.
"They serve as the gateway into and out of tumors and have been the focus of intense research in vascular and cancer biology. These findings bring these two fields together to add greater insight into control of cancer and metastases," he added.
Cancer cells build tiny structures, referred to by the scientists as "bridges," which allow them to make the necessary transfers needed for metastasis. To do this, transportable cells find their way into blood vessels, where they transform into circulating tumor cells (CTCs) and then locate areas in the wall of a blood vessel to attach themselves, perforate the lining and find new areas to grow into tumors — all of this despite the fact that endothelial cells are usually resistant to foreign-invading cells. However, endothelial cells do have an Achilles heel — they become defunct when cancer cells administer signals, which transform them into receptive entities. Hence, a bridge.
The scientists, who observed this behavior with the help of microscopy, deduced that finding a way to block this cellular broadcast could lead to halting the transfers altogether.
"Once we saw that these structures allowed for a ubiquitous transfer of a lot of different materials, microRNAs were an obvious interesting molecule because they're able to very broadly control the genome of a cell in ways that we don't really understand," said Yamicia Connor, a graduate student in the Harvard-MIT Division of Health Sciences and another member of the team. "That became our focus."
The researchers then noticed that an injection of microRNA to make the endothelial cells "sticky," enabling CTCs to connect to them by attracting other proteins, allowed for the construction of nanobridges. To prevent this process, they noted drugs that mess up the makeup of actin, one of the proteins that allow connective bridges to form and for transfers to happen.
The findings are a key step in developing drugs that will do this.
"If we can first understand how these structures are formed, then we can try to design targeted therapies to inhibit their formation, which could be a promising new area for developing drugs that specifically target metastasis," Connor concluded.
Source: MIT
