“These cells coordinate the entire cancer process,” said Paul Khavari, MD, Ph.D., professor and chair of dermatology and the Carl J. Herzog Professor in Dermatology in the School of Medicine. “They are highly mobile and highly invasive, and they gather at the edges of the tumor to lead the charge into surrounding tissue. But until now, we didn’t even know they existed.”
Blocking these cancer masterminds’ communication abilities significantly slowed the growth of human tumor cells transplanted into laboratory mice, suggesting that similar targeted therapies may one day be successful in human cancers.
A paper describing the research was published online June 23 in Cell. Khavari is the senior author. Postdoctoral scholar and clinical instructor Andrew Ji, MD; former graduate student Adam Rubin, Ph.D.; postdoctoral scholar Sizun Jiang, Ph.D.; and Kim Thrane, a graduate student at the KTH Royal Institute of Technology in Sweden, share lead authorship of the study.
Common Skin Cancer
For the study, the researchers focused on a common skin cancer called squamous cell carcinoma, which affects more than 1 million people each year in the United States. Although most people are treated successfully, about 1% will eventually die from the disease. Squamous cell carcinoma belongs to a class of cancers known as epithelial cancers, which includes about 90% of all human cancer types.
To understand more about how epithelial cancers grow and metastasize, Khavari and his colleagues combined several techniques to analyze the architecture, cell types and gene expression profiles at the single-cell level of squamous cell carcinomas from 10 people — in effect, not just generating a molecular fingerprint for each cell but also precisely locating it and its neighbors within the three-dimensional space of the growing tumor.