Single-Cell Transcriptome of Tumor-educated Lung epithelial cells
Ontology highlight
ABSTRACT: We performed single-cell RNA sequencing on epithelial cells, isolated from lungs of normal and tumor-bearing mice, to shed light on the function and phenotype changes of lung epithelial cells in pre-metastatic niche.
Project description:We performed transcriptome sequencing on epithelial cells, isolated from lungs of normal and tumor-bearing mice, to shed light on the function and phenotype changes of lung epithelial cells in the pre-metastatic niche.
Project description:To determine the influence of primary tumors on pre-metastatic lungs, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of alveolar type II epithelial cells (AT-II) in TLR3 deficient mice (Tlr3-/-) and wide-type (WT) littermates with tumor bearing. We subcutaneously inoculated Tlr3-/- and WT mice with Lewis lung carcinoma (LLC). Two weeks later, lung tissues from Tlr3-/- and WT mice were dissociated and AT-II cells were sorted. AT-II cells from mice without tumor bearing were set as controls. Primary tumor induced gene expression in AT-II cells from Tlr3-/- and WT mice was measured at 2 weeks after tumor inoculation subcutaneously. AT-II cells from mice without tumor bearing were set as controls.
Project description:To determine the influence of primary tumors on pre-metastatic lungs, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of alveolar type II epithelial cells (AT-II) in TLR3 deficient mice (Tlr3-/-) and wide-type (WT) littermates with tumor bearing. We subcutaneously inoculated Tlr3-/- and WT mice with Lewis lung carcinoma (LLC). Two weeks later, lung tissues from Tlr3-/- and WT mice were dissociated and AT-II cells were sorted. AT-II cells from mice without tumor bearing were set as controls.
Project description:We used our novel Cherry-niche system to specifically isolate cells from the metastatic niche of 4T1 lung metastasis and compared their profile with the one obtained isolating lungs cells distal from the tumour growth.
Project description:We used our novel Cherry-niche system to specifically isolate cells from the metastatic niche of 4T1 lung metastasis and compared their profile with the one obtained isolating lungs cells distal from the tumour growth
Project description:To profile the molecular changes in the lung during osteosarcoma pre-metastatic niche formation, we performed RNA-seq of lungs harvested from D0 and D14 after orthotopic implantation of K7M2 cells in balb/c mice.
Project description:Cancer cell behaviour is strongly influenced by the surrounding cellular environment, making the characterization of the local tumour microenvironment (or niche) a fundamental question in tumour biology. To date, a direct investigation of the early cellular changes induced by metastatic cells within the surrounding tissue is difficult to achieve, especially at early micro-metastatic stages and for low frequency niche populations. Here we present the strategy whereby metastatic cancer cells release a cell-penetrating fluorescent protein that is efficiently taken up by neighbouring cells, allowing spatial identification of the local metastatic cellular environment within the whole tissue. Notably, this strategy can be used to follow metastatic niches from early micro-metastasis to late macro-metastasis, allowing temporal resolution. Moreover, the presence of low represented niche cells can be detected and characterized among the bulk tissue. To highlight its potential, we have used this niche-labelling strategy to study the lung metastatic environment of breast cancer cells. We uncover the presence of lung parenchymal cells within the metastatic niche where lung epithelial cells show stem cell-like features with expression of lung progenitor markers, multi-lineage differentiation potential and self-renewal activity. Moreover, lung epithelial cells can be directly perturbed by cancer cells in ex vivo co-culture assays and support their growth. In summary, here we describe a novel labelling system that enables spatial resolution of the metastatic microenvironment and provide evidence that the tissue cellular environment surrounding metastatic growth is characterized by undifferentiated features. The data highlight the significant potential of this method as a platform for new discoveries.
Project description:Epithelial-mesenchymal transition (EMT) is a highly conserved morphogenic process defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. EMT is associated with increased aggressiveness, invasiveness, and metastatic potential in carcinoma cells. To assess the contribution of extracellular vesicles following EMT, we conducted a proteomic analysis of shed microvesicles released from Madin-Darby canine kidney (MDCK) cells, and MDCK cells transformed with oncogenic H-Ras (21D1 cells).
Project description:Metastasis of tumors to LNs predicts disease progression and poor outcomes of patients. Recent studies revealed that tumor cells deliver EVs to particular targeted recipient cells in draining LNs and subsequently alter their gene expression patterns to create a supportive pre-metastatic niche to promote LN metastasis. Yet, the biological role and underlying mechanism of bladder cancer derived EVs (BCa derived EVs) in mediating lymphatic pre-metastatic niche formation remain unclear. The present study aim to explore the differential genes of BCa derived EVs educated draining LNs and underlying mechanism in the lymphatic pre-metastatic niche formation.