Mesenchymal stem cells promote erlotinib resistance in non-small cell lung cancer through the HGF-AKT/ERK1/2-OPN pathway

OBJECTIVES: To investigate the mechanisms by which mesenchymal stem cells (MSCs) contribute to erlotinib resistance in non-small cell lung cancer (NSCLC). METHODS: validation, a xenograft model was established by co-injecting HCC827 cells and MSCs into NOD/SCID mice. RESULTS: , tumors derived from co-injected MSCs and HCC827 cells exhibited significantly greater volume and weight after erlotinib treatment compared to control tumors. CONCLUSIONS: This study identifies a novel MSC-mediated resistance mechanism in which MSC-derived HGF activates compensatory AKT/ERK1/2 signaling, circumventing EGFR blockade by erlotinib. Concurrent upregulation of OPN in NSCLC cells forms a synergistic survival axis under erlotinib pressure. These findings suggest that targeting MSC-derived HGF and tumor-derived OPN may offer promising strategies to overcome erlotinib resistance in NSCLC.