In Vivo Tagging of Lung Epithelial Cells to Define the Early Steps of Tumor Cell Dissemination
Annual rept. 15 Sep 2013-14 Sep 2014
TRUSTEES OF BOSTON UNIV MA
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To understand the early events that accompany invasive behavior in vivo, we proposed to develop a lineage-labeling system to detect and isolate cells of lung epithelial origin during tumor progression in a mouse model of lung cancer. A mouse model of lung cancer with metastasis LSL-KrasG12DLkb1LL mice was interbred with Nkx2.1-CreERT2 knock-in mouse strain, containing a tamoxifen-inducible lineage specific Cre recombinase, to generate adult lung-specific mutations in Kras and Lkb1. We introduced a RosaYFP lox-stop-lox-YFP into the mutant background to specifically label and track lung epithelial cells during tumor progression and metastasis. This model Kras G12D Lkb1LLYFPL-Nkx2-1creER2- mice, will allow us to determine the timing of dissemination during the natural evolution of lung adenocarcinoma in vivo and correlate cell phenotype with the acquisition of invasive and tumor-initiating properties. We will test our hypothesize in year 2 NCE that 1 lung tumor cells invade and disseminate early in tumor evolution via EMT and 2 disseminated cancer cells exhibit a stem cell-like phenotype. Successful completion of this project promises to shift the current paradigm of lung cancer metastasis and will aid in early detection, and novel treatment approaches.
- Medicine and Medical Research