| Literature DB >> 24794706 |
Chunxiao Xu1, Christine M Fillmore2, Shohei Koyama3, Hongbo Wu4, Yanqiu Zhao4, Zhao Chen1, Grit S Herter-Sprie1, Esra A Akbay1, Jeremy H Tchaicha1, Abigail Altabef1, Jacob B Reibel1, Zandra Walton5, Hongbin Ji6, Hideo Watanabe7, Pasi A Jänne1, Diego H Castrillon8, Anil K Rustgi9, Adam J Bass10, Gordon J Freeman11, Robert F Padera12, Glenn Dranoff3, Peter S Hammerman13, Carla F Kim14, Kwok-Kin Wong15.
Abstract
Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that biallelic inactivation of Lkb1 and Pten in the mouse lung leads to SCC that recapitulates the histology, gene expression, and microenvironment found in human disease. Lkb1;Pten null (LP) tumors expressed the squamous markers KRT5, p63 and SOX2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. SCA1(+)NGFR(+) fractions were enriched for tumor-propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and NGFR(+) cells in human SCCs highly expressed Pd-ligand-1 (PD-L1), suggesting a mechanism of immune escape for TPCs.Entities:
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Year: 2014 PMID： 24794706 PMCID： PMC4112370 DOI： 10.1016/j.ccr.2014.03.033
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743