10X genomics single cell RNA sequencing of tumor sections from tumor bearing KrasG12D/+Lkb1fl/fl(KL) mice after Ad-cre injection for 10 weeks
Ontology highlight
ABSTRACT: Tumor-infiltrating cells comprise many celltypes, including monocytes, macrophages, dendritic cells, neutrophils, stromal cells and epithelial cells, and have emerged as key regulators of cancer growth. These cells can diversify into a spectrum of states, which may promote or limit tumor outgrowth, but remain poorly understood. Here, we used single-cell RNA sequencing to map cell heterogeneity in non-small cell lung cancer mouse model. We uncovered 11 cell types in tumor sections, most of which were reproducibly found across tumor bearing mice. we obtained a series of genes which expression levels were very low, such as cytokines and chemokines. It is very helpful for us to understand the signal cascade and ligands-receptors interaction between different cell types.
Project description:LKB1 deficiency is widely acknowledged to induce immune-desert tumors in the non small cell lung cancer. Dissecting the "cold" tumor microenvironment (TME) would promote a better understanding of mechnism of the immune evasion triggered by LKB1 loss, thereby facilitating to seek therapeutic targets. Here, we exploited single-cell RNA sequencing to show the immune landscape of genetically engineered mouse model (GEMM) bearing a conditional activating mutation of endogenous Kras (KrasLSL-G12D/+) with or without Lkb1 conditional knockout (Lkb1fl/fl). The heterogeneity of TME and celler communication were analyzed.
Project description:10X genomics single cell RNA sequencing of tumor sections from tumor bearing KrasG12D/+Lkb1fl/fl(KL) mice after Ad-cre injection for 10 weeks
Project description:Ribosome profiling on sections taken from a kidney tumor For two tumors: 2 sections of normal tissue and 4 samples of tumor tissue, for another two tumors 1 section of normal tissue and 1 section of tumor tissue
Project description:The study will enroll patients with metastatic colorectal cancer receiving chemotherapy. A total of approximately 22 cc of blood will be drawn during various chemotherapy infusions. Additional proposed laboratory studies may unravel important biological insights into the relationship of circulating tumor cell genomic and genetic profiles as they compare to the primary tumors. Additionally the investigators hope to gain an understanding of potential subgroups of patients that have very high numbers of circulating tumor cells or those with early relapse of circulating tumor cells after early reduction of circulating tumor cell numbers.
Project description:Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state, as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. Comparison of tissue proteomics data with all those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1 and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.
Project description:Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state, as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. Comparison of tissue proteomics data with all those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1 and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.
Project description:Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state, as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. Comparison of tissue proteomics data with all those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1 and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.