Inhibition of Ron kinase blocks conversion of micrometastases to overt metastases by boosting anti-tumor immunity
Menée à l'aide de modèles murins, cette étude suggère l'intérêt des inhibiteurs de Ron, le récepteur de la protéine de stimulation des macrophages, pour prévenir la transformation de micrométastases en métastases
Many "non-metastatic" cancers have spawned undetectable metastases prior to diagnosis. Eventual outgrowth of these microscopic lesions causes metastatic relapse and death, yet the events that dictate when and how micrometastases convert to overt metastases are largely unknown. We report that macrophage stimulating protein (MSP) and its receptor, Ron, are key mediators in conversion of micrometastases to bona fide metastatic lesions through immune suppression. Genetic deletion of Ron tyrosine kinase activity specifically in the host profoundly blocked metastasis. Our data show that loss of Ron function promotes an effective anti-tumor CD8+ T cell response, which specifically inhibits outgrowth of seeded metastatic colonies. Treatment of mice with a Ron-selective kinase inhibitor prevented outgrowth of lung metastasis, even when administered after micrometastatic colonies had already been established. Our findings indicate that Ron inhibitors may hold potential to specifically prevent outgrowth of micrometastases in cancer patients in the adjuvant setting.