Accession Number : ADA614401


Title :   In Vivo Tagging of Lung Epithelial Cells to Define the Early Steps of Tumor Cell Dissemination


Descriptive Note : Annual rept. 15 Sep 2013-14 Sep 2014


Corporate Author : TRUSTEES OF BOSTON UNIV MA


Personal Author(s) : Kathuria, Hasmeena


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a614401.pdf


Report Date : Oct 2014


Pagination or Media Count : 10


Abstract : 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-KrasG12D/Lkb1L/L 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 /Lkb1L/L/YFPL/-/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.


Descriptors :   *CELLS(BIOLOGY) , *NEOPLASMS , EPITHELIUM , GENES , IN VIVO ANALYSIS , LUNG CANCER , METASTASIS , MICE , MODELS , MUTATIONS


Subject Categories : Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE