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: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: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.
Project description:Pancreatic cancers (PCs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PC-derived exosomes induce liver pre-metastatic niche formation in naïve mice and consequently increase liver metastatic burden. Uptake of PC-derived exosomes by Kupffer cells caused transforming growth factor β secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared to patients whose pancreatic tumors did not progress, MIF was markedly higher in exosomes from stage I PC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PC liver metastasis.
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-educated mesenchymal stem cells promote pre-metastatic niche formation for disseminated cancer cells via the induction of PMN-MDSC expansion
Project description:This experiment looks at the dissection of the microenvironment in the lung metastatic niche in a model of murine triple-negative breast cancer as disease progresses. Mice received an orthotopic inoculation of 4T1 cells and disease was allowed to progress for 7, 14, or 21 days correlating to the pre-metastatic, micro-metastatic, and metastatic niche, respectively. Healthy controls were obtained along with each time point.
Project description:Through an integrated transcriptome analysis of orthotopic colorectal cancer tumor-bearing mice and sham-operation mice, we showed the distinct immune microenvironment of pre-metastatic liver and identified MDSCs as the dominated cell type mediating pre-metastatic niche formation. MDSCs instead of other immune cell types were highly infiltrated in the pre-metastatic liver when compared with normal liver. Notably, immunosuppressive factors released by MDSCs such as HIF1α, iNOS, TGFβ were significantly up-regulated in the pre-metastatic liver. Increasing immune checkpoint molecules expression also reflected an immunosuppressive condition of pre-metastatic liver. The primary tumor may induce MDSCs accumulation via metabolic mechanism including glycolysis/gluconeogenesis, HIF-1 signaling pathway, and CCL28 chemokine axis. This study depicts the immune cell landscape of pre-metastatic cancer and primary CRC tumor, and provides insights into how MDSCs reshape the pre-metastatic niche facilitating circulating cancer cells colonization.