Abstract 2290: More than a biomarker: Studying the role of vimentin in lung cancer metastasis

Abstract

Abstract A major mechanism of metastasis is the epithelial to mesenchymal transition (EMT) where epithelial cells from the primary site undergo genetic and epigenetic alterations to become motile and mesenchymal. A canonical marker of EMT and a clinical marker of metastasis is the intermediate filament protein, vimentin. Vimentin expression correlates with increased metastatic potential and poor patient prognosis across most solid tumor types including lung, prostate, and breast cancers; however little is known about how vimentin functions to promote the metastatic cascade. Here we use a lung cancer mouse model to study the role of vimentin in lung cancer metastasis in vivo. We have re-developed an LSL-KrasG12D,LKB1fl/fl mouse model whereby intranasal administration of lentiviral Cre recombinase causes a KrasG12D mutation and LKB1 knockout in the lungs. Consequently, about half of the mice that develop primary lung tumors after 10 weeks also develop metastasis to the mediastinal lymph nodes by week 16. We crossed this mouse with a Vim-/- mouse to create a LSL-KrasG12D,LKB1fl/fl, Vim-/- (termed here KLV) mouse to determine if loss of vimentin prevents lung cancer metastasis in this model. Our findings show that the KLV mouse exhibits significantly less metastasis to the mediastinal lymph nodes (12%) as compared with its vimentin wild type counterpart but does not show a decrease in primary tumor formation. These knockout mice also exhibit less focal invasion at the primary tumor site while maintaining a well-differentiated adenocarcinoma histology independent of vimentin genotype. Taken together, our work indicates that vimentin is critical for lung cancer metastasis but not primary tumor formation. Citation Format: Alessandra M. Salgueiro, Melissa Gilbert-Ross, Lauren S. Havel, John Shupe, Adam I. Marcus. More than a biomarker: Studying the role of vimentin in lung cancer metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2290. doi:10.1158/1538-7445.AM2015-2290