When multiple myeloma cells are taken out of the bone marrow environment, they typically die. The communication between the myeloma cells and the bone marrow is a key factor in keeping multiple myeloma alive and helping myeloma cells grow. But what if that cross-talk could be silenced?

Myeloma researchers from the University of Milan discovered one of the ways that the conversation could be quieted. They found that by blocking an oncogene (a gene that can turn a cell into a cancer cell) called NOTCH2, they could stop the interplay between tumor and bone marrow. 

The researchers found that the communication between myeloma cells and the bone marrow doesn't just rely on direct cell to cell communication, but an important function is performed by myeloma-derived extracellular vesicles (EVs). These EVs deliver proteins, metabollites and nucleic acids (like DNA and RNA) to cells. They also regulate cancer cell death, cancer cell proliferation and they affect signaling pathways, playing an important role in cancer development.  EVs are like a cargo transport that take RNA messages from one cell to another.

NOTCH2 receptors are part of these EV cargo and can promote myeloma cell growth in two important ways. The first is tumor angiogeneis, or the growth of vessels important for oxygen and nutrients needed for tumor growth. The second is the stimulation of the bone marrow cells called osteoclasts, cells that break down and destroy bone (hence the bone lesions in multiple myeloma). 

Preventing NOTCH2 expression in myeloma cells can decrease their cancer growth potential. 

According to University of Milan researcher Rafaella Chiaramonte: 

“Silencing the NOTCH2 gene with RNA molecules (shRNA) in myeloma cells, we have verified for the first time that it is possible to block the transfer of oncogene NOTCH2 through the extracellular vesicles, thus inhibiting their pathological effects. The results obtained open the way to the design of new therapeutic strategies based on RNA drugs, aimed at counteracting the pathological effects of extracellular vesicles in multiple myeloma and in other types of cancer.”

If cargo is being delivered by these EV cells, the researchers want to ensure that it is delivering anti-myeloma cargo.