Scientists Uncover Why Skin Cancers Vary in Aggressiveness by Location
Key Finding: The surrounding tissue's fat metabolism determines how dangerous a squamous cell carcinoma becomes.
Researchers from the Universities of Manchester and Liverpool have identified the reason why squamous cell carcinomas (SCC) behave so differently depending on where they develop in the body. The study, published in Nature Metabolism, reveals that fibroblasts in the surrounding tissue exhibit distinct fat metabolism patterns that directly influence cancer cell behavior.
How Fat Drives Cancer Invasion
The research found striking differences in how tumors interact with their environment:
- In oral cancers: Fibroblasts supply sphingomyelins, which activate the ceramide/S1P/STAT3 pathway, driving aggressive invasion.
- In lung cancers: Fibroblasts transfer triglycerides, stimulating cholesterol production and leading to highly invasive behavior.
- In skin cancers: Skin fibroblasts contain fewer fats, making cutaneous SCC significantly less invasive.
Expert Commentary
Dr Amaya Viros (University of Manchester): "The tumour microenvironment, particularly fibroblasts and the fats they produce, plays a decisive role in determining how dangerous a particular SCC will become."
Dr Timothy Budden (University of Liverpool): "Targeting these fat-driven interactions could slow or halt the spread of oral and lung SCC, offering new hope for patients."
Potential for Drug Repurposing
Dr Viros noted that existing drugs for lipid disorders, such as statins, could potentially be repurposed for aggressive epithelial cancers. "This opens up the possibility of using well-established, safe medications to target a previously unrecognized vulnerability in these cancers."
Study Support
The research was funded by Cancer Research UK, NIHR Manchester BRC, and The Royal Marsden NHS Foundation Trust and Institute of Cancer Research.