Inhibition of ron kinase blocks conversion of micrometastases to overt metastases by boosting antitumor immunity.

ABSTRACT: Many "nonmetastatic" cancers have spawned undetectable metastases before 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 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 antitumor CD8(+) T-cell response, which specifically inhibits outgrowth of seeded metastatic colonies. Treatment of mice with a Ron-selective kinase inhibitor prevented outgrowth

SUBMITTER: Eyob H 

PROVIDER: S-EPMC3710539 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature