Karuna Ganesh, MD, PhD (Clinical Investigator ’19-’22), is tackling one of the most pressing clinical problems in oncology—metastasis, which is responsible for about 90 percent of cancer deaths. She and her colleagues at Memorial Sloan Kettering Cancer Center have discovered a novel framework for approaching metastasis and developing treatments. The researchers found that metastasis-initiating cells can hijack the body’s natural wound-healing abilities to colonize distant organs.
The team focused on a cell surface molecule called L1CAM that is necessary for many different cancer cells to successfully metastasize. Neurons normally use this sticky molecule to crawl to the proper location in the brain and sprout branches during brain development.
Dr. Ganesh has shown that L1CAM is also found on both metastatic colon cancer cells and normal gut cells that are repairing tissue damage following colitis, inflammation in the intestine. Why would metastasis-initiating cells share a marker of wound healing? To answer this question, Dr. Ganesh used fresh samples of metastatic colorectal tumors to grow three-dimensional tumor organoids in the lab.
Using these tumor organoids, she observed that separating cells from their neighbors was enough to trigger L1CAM production. Once detached from their neighbors, metastasizing cells adopt a migratory behavior to reach new locations similar to wound healing cells. During normal healing, cells move into the injury and make new tissues, but during metastasis this same process enables cancer cells to detach and colonize new destinations.
This study suggests that stem cells forming primary tumors are fundamentally different from the ones that form secondary tumors in new organs in the body. The researchers are currently looking for drugs that might block L1CAM and thereby rob cancer cells of their ability to metastasize.
This research was published recently in Nature Cancer.
Read more : What does cancer metastasis have to do with wound healing? Also in The Scientist.
