WashU Medicine researchers at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, along with colleagues at the Weizmann Institute of Science in Israel, have found that aggressive cancer cells can appear in different locations within head and neck tumors, providing new clues as to why some such cancers — particularly squamous cell carcinomas not caused by the human papillomavirus (HPV) — are more difficult to treat.
In research published Aug. 14 in Nature Genetics, the researchers found two distinct spatial patterns, or locations, where aggressive cancer cells can occur. One location, which was previously known, is at the outer edge of a tumor as cells begin to invade surrounding tissue. The newly discovered location is within the core of some tumors.
“Understanding the complex tumor ecosystem with spatial approaches is emerging as a critical tool to study cancer more broadly,” said Sidharth Puram, MD, PhD, FACS, the Lindburg Professor and head of WashU Medicine’s Department of Otolaryngology — Head & Neck Surgery and senior author of the study. “By using these techniques, we can understand the components of the tumor, but also where those cells are from. In this case, we were quite surprised to see these aggressive cancer cells, which we call partial epithelial-to-mesenchymal transition, or EMT, in different locations. It completely upended our views on head and neck tumors.”
Head and neck cancers are the sixth most common cancer worldwide, and there is increasing evidence that HPV is strongly associated with a subset of these cancers — particularly oropharyngeal cancers, which include cancers of the tonsils and the surrounding area in the middle part of the throat. The team of researchers studied tumors from patients diagnosed with HPV-positive, as well as HPV-negative, head and neck squamous cell carcinoma.
By closing mapping where different cells reside within the tumors, the researchers discovered aggressive cancer cells deep inside the tumors of some patients. Further study found that these deeper cancer cells appeared to take on a more aggressive state after interacting with certain immune cells, in response to signals involving a protein called Oncostatin M (OSM).
Puram explained that when these aggressive cells were at the edge of a tumor, they were activated by signals from fibroblast cells, which are part of a tumor’s structural elements. However, in the core these aggressive cells were typically found in proximity to concentrations of immune-response macrophage cells that normally digest cellular waste products and foreign substances. These macrophages release the activating OSM signal.
“This distinction is critical, as we must target these triggers differently in edge versus core tumors,” he said. “Fortunately, in each case, there are therapeutic agents that are being developed.”
While most of the aggressive cells were present at the edge, up to one-third had the more distinct core pattern of distribution in HPV-negative cancers. Notably, Puram said, “We are trying to understand how these different locations affect tumor response to treatment and patient outcomes.”
If researchers can figure out how to block the signal or signals that make these cancer cells more aggressive, it could lead to potential new treatment strategies for head and neck cancers. Right now, the research is in its early stages.
“It’s a clue,” Puram stressed. “We have an important clue that increases our understanding of how head and neck cancers potentially behave and spread. But it’s significant because it may lead to the development of more effective options to treat some of the most difficult forms of this type of cancer.”
