Abstract IA14: Inhibition of Ron kinase blocks conversion of micrometastases to overt metastases by boosting antitumor immunity

Abstract

Abstract Many “non-metastatic” cancers have spawned clinically undetectable metastatic colonies even prior to diagnosis. Eventual outgrowth of these microscopic lesions is the cause of metastatic relapse and death from cancer, yet the events that dictate when and how disseminated cancer cells convert to overt metastasis are largely unknown. We utilized mouse genetics and tissue complementation strategies in a murine model of spontaneous metastasis to interrogate the role of macrophage stimulating protein (MSP) and its receptor, Ron, in metastasis. Our data reveal the MSP/Ron pathway as a key mediator 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. Citation Format: Alana Welm. Inhibition of Ron kinase blocks conversion of micrometastases to overt metastases by boosting antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA14.