Giant-Nucleus Kidney Cells Signal Early-Stage Cancer, Study Finds

Iron is an essential nutrient, but too much of it damages cells and raises cancer risk. A team at Nagoya University Graduate School of Medicine in Japan has shown that surviving cells with an abnormally large nucleus form the foundation of early-stage cancer after iron-induced damage. These giant-nucleus cells could serve as an easy-to-spot early cancer indicator, the team says, since they are simple to identify under a microscope. The findings appear in the journal Redox Biology.

Lead author Shinya Toyokuni, professor emeritus at Nagoya University, said scientists have seen such large-nucleus cells in early oxidative-stress-driven cancer since the 1980s, but their role was unclear. Toyokuni, Assistant Professor Yingyi Kong and colleagues injected ferric nitrilotriacetate, a cancer-causing iron compound, into wild-type rats and rats carrying a mutated BRCA1 gene, a DNA-repair gene, to damage their kidneys, then collected tissue before and one and three weeks after. They mapped gene activity in individual cells using spatial transcriptomics.

Giant-nucleus cells appeared within one week, showing higher activity of the cancer genes Myc and Met and resistance to ferroptosis, an iron-dependent form of cell death. BRCA1-mutant rats developed giant-nucleus cells with different profiles than wild-type rats, suggesting impaired DNA repair let more precancerous cells survive. Even normal-looking neighboring cells showed gene changes that may aid survival. BRCA1-mutant kidneys also had far more stromal cells -- non-cancerous immune and connective-tissue cells -- around damaged areas.

The team sorted giant-nucleus cells into six types by gene activity and nuclear shape; one type, more common in BRCA1-mutant kidneys, showed higher cancer-gene activity, a potential precancerous state. Comparing results with TCGA-KIRC, a public kidney cancer database, patients whose tumors matched the cancer-prone pattern had shorter survival.

In a small pilot study, similar abnormal nuclei appeared in breast tissue from seven people with inherited BRCA1 mutations, versus 15 without. The researchers said long-term studies are needed to determine whether the findings can help diagnose kidney cancer.