Cancer cells acquire cysteine directly from a reduced tumor microenvironment

Lung tumor microenvironments in three mouse cancer models are chemically reduced, with free cysteine predominating and cystine nearly absent in the lung TME.

• Why it matters: Tumor redox conditions are poorly defined, limiting how accurately cancer metabolism and oxidative-stress vulnerabilities are modeled in vitro.
• What they did: Sulfur metabolites were measured in tumor interstitial fluid, matched healthy organs, and serum; lung cancer cells then showed cysteine/cystine uptake and growth on cysteine alone.
• The result: In a lung-TME-matched medium, cells became independent of cystine import through xCT and were resistant to glutaminase inhibitors, oxidants, and ferroptosis inducers while maintaining NADPH under oxidative challenge.