Michael Clarke, MD

January 6, 2023

By Christopher Vaughan

Most deaths from breast cancer result not from the growth of the primary tumor in the breast, but from the growth of satellite, metastatic tumors that break off from the original tumor and make new homes in the bone, brain or other tissues. But stopping the spread of breast cancer to other tissues has been a challenge because it has not been clear which cells in the tumor are responsible for metastases and how they manage to spread. 

Now researchers at the Institute for Stem Cell Biology and Regenerative Medicine have combined powerful analytical techniques from cellular biology and biomedical data science to identify a population of breast cancer cells that can metastasize and to pin down how the cells do this. The work offers a possible target for potential drugs that may be able to stop breast cancers from spreading, turning a deadly cancer into a manageable one. 

The paper was published in the journal Science Advances. Institute members Michael Clarke, MD and Aaron Newman, PhD are co-senior authors on the paper. Clarke is the Karel H. and Avice N. Beekhuis Professor of Cancer Biology. Newman is an assistant professor in the department of biomedical data science. Co-first authors on the paper are Shaheen Sikandar, PhD; Gunsagar Gulati, PhD; and Jane Antony, PhD. Institute members Phillip Beachy, PhD and Kristy Red-Horse, PhD, were also involved in the research.

Not all cancer cells can be the seeds that start new tumors. Such cells need to have the qualities of stem cells—ie, they need to be immature and should be able to reproduce themselves as well as produce more mature cancer cells. The researchers analyzed single cell data from breast cancer patients using CytoTRACE, a tool developed by Newman.With CytoTRACE, they found a suspect population that was not only relatively less mature than other cells in the breast tumor, but it was even more interesting because these cells also express the hematopoetic stem cell factor, LMO2.

“LMO2 is  well-studied as a gene involved in hematopoiesis (the generation of blood and immune cells) and leukemia, but it is not usually thought of as being important in breast cancer,” said Sikandar. “We asked, ‘what is it doing here?’”

Further investigation piqued the researchers’ interest more. They found that breast tumors that expressed LMO2 were much more likely to metastasize and in patients more likely to have negative outcomes. 

LMO2’s connection with both leukemia and breast cancer was highly suggestive, but misleading in some ways. “It turned out that LMO2 is doing very different things in leukemia and breast cancer, and we spent a lot of time going down dead ends,” Sikandar said. “LMO2 is not helping make more breast tumor cells like it is in leukemia, but is needed for breast cancer cells metastasize.”

Cells that express LMO2, the researchers say, simply become more mobile, changing in ways that help them get into the bloodstream and then exit the bloodstream to seed a new cancer tumor somewhere else. 

“We suspect that even the outside of the LMO2+ breast cancer cells changes to resemble vascular cells, so they are able to attach and move through the blood vessels that lace the tumor.” 

The researchers have great hope that this discovery could lead to new drugs to control breast cancer. An effective inhibitor that is able to block LMO2 might keep breast cancer from metastasizing, giving doctors more time to eradicate the primary tumor and a better chance to cure the cancer.