While some oral cancer patients experience metastasis and others do not, a research team including Hirosaki University has revealed that the determining factor lies in a specific cell population called "myCAF" (myofibroblastic cancer-associated fibroblasts) located near cancer cells. They also discovered that metastatic patients exhibit characteristic expression patterns in 23 genes. Although oral cancer has a good prognosis when detected early, some patients develop lymph node metastasis for previously unknown reasons. If this research can be applied to clinical testing, it could contribute to personalized medicine approaches such as genomic medicine.
Oral cancer is believed to develop from alcohol consumption, smoking, and ill-fitting dental prosthetics that irritate the oral mucosa. It is often discovered during workplace dental examinations or when patients visit dental clinics complaining that "mouth ulcers don't heal after two weeks." With established treatment methods including surgery and chemotherapy, the overall five-year survival rate reaches 60-70%. However, some patients develop lymph node metastasis, causing survival rates to drop dramatically. The factors causing this "turning point" remained unknown.
An international collaborative research group led by Visiting Researcher Ken Furudate, who studies oral surgery and bioinformatics at the Department of Dentistry and Oral Surgery, Graduate School of Medicine at Hirosaki University, and Dr. Koichi Takahashi, who studies genomic medicine and oncology at the University of Texas MD Anderson Cancer Center conducted "spatial transcriptome analysis" to visualize cancer cells like a map, investigating which cells function where and how.
The results showed that in patients who develop oral cancer metastasis, myCAF, a specific type of cancer-associated fibroblast found in tumors, becomes activated. myCAF is a type of cancer-associated fibroblast that exists in other solid cancers as well. While it worsens tumors in many cancers, it suppresses progression in pancreatic cancer, and its function remains largely mysterious.
Provided by Hirosaki University
Detailed investigation of myCAF function revealed that myCAF sends proliferation-promoting signals to adjacent cancer cells in the extracellular matrix, a cellular "scaffold" made of collagen and other components. This activation causes cancer cells that would normally remain "quiet" at the boundary between tumor and normal cells to become activated cancer stem cells, developing treatment resistance and metastatic capabilities.
Furthermore, examination of gene expression and mutation patterns in patients who developed oral cancer metastasis revealed differences in 23 genes compared with patients without metastasis. If genomic medicine advances, examining the expression patterns of these genes when oral cancer is diagnosed could contribute to predicting whether metastasis will occur. Furudate stated, "Further elucidation of metastatic mechanisms will lead to improved survival rates. We will continue our research to make oral cancer a curable disease."
This research was conducted with support from the Japan Society for the Promotion of Science's Grants-in-Aid for Scientific Research program and grants from the Uehara Memorial Foundation. The results were published in the online edition of the American scientific journal PLOS Genetics on the 5th of September and announced by Hirosaki University on the same day.
Original article was provided by the Science Portal and has been translated by Science Japan.