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:Pre-metastatic niche (PMN) formation is a critical step in metastatic progression, yet the biological effect of subtherapeutic-dose of ionizing radiation (SDIR) following radiotherapy on this process remains unclear. Using a 4T1 breast cancer mouse model, we investigated the effects of SDIR (3×0.3 Gy) on lung PMN development and metastasis formation. Lung PMNs were exposed to SDIR on days 8–10 post-tumor induction, followed by mastectomy on day 18, and analyzed on day 24. SDIR significantly increased total metastatic volume (TMV) in lungs, suggesting an accelerated PMN formation. Mechanistically, SDIR upregulated Bv8 expression, enhanced neutrophil recruitment, and increased MMP9, S100A8, and IL-6 production in the PMN by day 11, though differences between irradiated and non-irradiated PMN were no longer evident by day 14. Notably, Bv8 inhibition prevented SDIR-induced neutrophil recruitment but did not reduce TMV, indicating additional mechanisms in SDIR-driven metastasis. Proteomic analysis revealed SDIR-induced metabolic reprogramming, extracellular matrix (ECM) remodeling, and upregulation of adhesion-related pathways, driving a microenvironment that accelerates tumor invasion and metastatic outgrowth. By demonstrating that SDIR reprograms the pre-metastatic lung microenvironment, this study highlights the need to integrate organ-specific radiation exposure into predictive models of metastasis and identifies metabolic and immune-stromal pathways as potential targets for therapeutic intervention.