Decoding Cancer Cross-Talk

While many aspects of metastasis have been mapped out, the mechanisms by which cancer cells travel from primary to secondary sites have never been fully understood. A new study by researchers at Brigham and Women’s Hospital helps fill the gap by tapping into the communication that allows cancer cells to induce healthy endothelium to become cancerous (1).

The researchers didn’t initially set out to study metastasis, according to principle investigator Shiladitya Sengupta, but rather to study the behavior of metastatic breast cancer cells in the presence of endothelial cells, which make up the blood vessels that sustain the tumor, “Normally breast cancer cells, when grown on a 3D tumor matrix, form spheroids called mammospheres. We had anticipated similar structures, with blood vessels growing towards the spheroids. However, when we introduced the cancer cells to the culture containing the blood vessels, the cancer cells didn’t form spheroids but instead aligned on the vascular network,” says Sengupta.

Surprised by their finding, the team used electron microscopy to investigate, and discovered nanoscale bridges linking the cancer cells to endothelium. Sengupta says, “This is a highly energy intensive process, and we rationalized that for the cancer cell to spend so much energy building the bridges, they might have a function. That’s how we started studying the communication angle.”

The team determined that the nanoscale bridges (composed of cytoskeletal elements) were actually used as a conduit for intercellular miRNA transfer to transform healthy endothelial cells into a pathological state. Sengupta explains that the cancer cells inject miRNAs to essentially hijack the endothelial cells. The team went on to identify chemical compounds that could break down the connections between cancer and endothelial cells, and found that mice given these compounds had reduced metastatic disease.

“We have only just scratched the surface,” says Sengupta. “We need to test if this behavior is ubiquitous. Are there any specific types of endothelial cells that attract such nanoscale bridges, or is it just a stochastic process? How is the information flow regulated? Much of the interesting science is still waiting to be explored.”