Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated 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 Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells. Kras tumor stroma cells and LP tumor stroma cells were sorted by FACS, the cells were gated as EpCAM-/CD45+/CD31+
Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated 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 Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells. Normal EpCAM+, Kras tumor EpCAM+ and LP tumor EpCAM+ were sorted by FACS, the cells were gating as EpCAM+/CD45-/CD31-
Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated 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 Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells.
Project description:Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that bi-allelic inactivation of Lkb1 and Pten in the mouse lung led to SCC that recapitulated 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 Pdl1, suggesting a novel mechanism of immune escape for TPCs. We used microarrays to detail the gene expression profles among lung SCC tumor epitheial cell, lung ADC tumor epithelia cell and normal epithelial cells.
Project description:In order to identify the contribution of Lkb1 loss to Pten driven prostate cancer progression, we engineered a prostate conditional mutant mice in which was induced the loss of Lkb1 in combination with heterozygous loss of the prostate tumor suppressor Pten (Ptenpc+/- Lkb1pc-/-). This mouse model developed metastatic prostate squamous cell carcinoma. We compared this tumor type with the adenocarcinomas developed in Ptenpc-/- Lkb1pc+/+ mice. We carried out microdissection and RNA extraction of tumor tissues embedded in paraffin of Ptenpc+/- Lkb1pc-/- and Ptenpc-/- Lkb1pc+/+. To distinguish between early and late phenotype of prostate squamous cell carcinoma, we compared Ptenpc+/- Lkb1pc-/- tumor tissues collected at the age of six and ten months of age among them and with Ptenpc-/- Lkb1pc+/+ mouse prostate tissue.
Project description:Lung cancer is the leading cause of cancer death in USA. Squamous Cell Carcinoma (SCC) is one of the subtypes of lung cancer. It is still largely unknown which genes or pathways regulate lung SCC development. Recently, we found JNK1/2 pathway was inhibited in mouse lung SCC induced by double ablation of Pten and Lkb1 in mouse lung epithelial cells. Now we aim to identify a genome-wide molecular signature of JNK1/2 signaling in mouse squamous cell carcinoma cells and determine pathways that transduce JNK1/2 signaling.
Project description:Lung cancer, majorly divided into non-small cell lung cancer (80-85%) and small cell lung cancer (15-20%), is the leading cause of cancer death in USA. Squamous Cell Carcinoma (SCC) is one of major subtypes of non-small cell lung cancer. Although genomic analysis of tumors from SSC patients have identified frequently mutated genes in these tumors, it’s still largely unknown which genes determine SCC development. Now we found that ablation of Lkb1 and Pten could induce SCC and ASC around 3 months of age. Therefore, transcriptome analysis of lung SCC and ASC of CCSPiCreLkb1f/f mice will help us understand how Lkb1 and Pten regulate the development of lung SCC and ASC.