Project description:Cancer-derived exosomes can deliver nucleic acids, proteins, and lipids to neighboring or distant cells and subsequently modulate recipient cells. Recently, high levels of microRNAs (miRNAs) have been identified in cancer-derived exosomes, which provide a favorable microenvironment that contribute to tumorigenesis, tumor metastasis, angiogenesis, chemoresistance, and immune escape. Howerer, the mechanism of the cancer-derived exosomes regulating CD45+EpCAM+ cell apoptosis remains unclear.
Project description:Exosomes (40–100 nm) are organelle-like membranous structures shed into interstitial spaces and body fluids under diverse pathophysiologic conditions, including tumor development. The tumor microenvironment is abundant with exosomes secreted by the cancer cells themselves. Studies have shown that tumor-derived exosomes can transport RNA and active molecules to other cells to promote tumor growth. Exosomes are increasingly being recognized as a major contributor in the progression of malignant neoplasms. We have found that normal melanocytes can acquire invasiveness through the internalization of melanoma cell-derived exosomes. However, little is known about how the exosomes modulate the melanocytes in the microenvironment to optimize conditions for tumor progression and metastasis. We hypothesize that melanoma cell-derived exosomes can drive the dysregulation of transcriptomes in normal melanocytes and facilitate melanoma progression. Our objective is to identify differentially expressed genes in melanocytes driven by tumor cell-derived exosomes through RNA sequencing and translate those genes as therapeutic targets for melanoma metastasis.
Project description:Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, we identified significantly higher levels of miR21 in exosomes and tissue lysate isolated from cancer associated adipocytes (CAA) and fibroblasts (CAF) compared to those from ovarian cancer cells. Functional studies and transcriptome analysis on miR21 transfected SKOV3 ovarian cancer cells revealed that miR21 could be transferred from CAA or CAF to ovarian cancer cells and modulate ovarian cancer apoptosis and chemoresistance through binding to its direct target APAF1. These data suggest that malignant phenotype of metastatic ovarian cancer cells can be modulated by miR21 delivered by exosomes derived from neighboring stromal cells in the omental tumor microenvironment.
Project description:Cancer cell-derived vesicles, so-called exosomes, are important means in cell-cell communication between tumor cells and the tissue microenvironment. Amongst others, exosomes harbor functional RNAs, which are transferred to recipient cells and alter the cellular phenotype of respective cells. Aim of the current study was a detailed characterization of the RNA composition of cancer-cell derived exosomes in CLL. Due to prior results showing an enrichment of small RNAs in exosomes, this was focused on profiling of small RNAs. Further, the impact of high abundant exosomal RNAs in phenotypic alterations of cells in the tumor microenvironment upon exosome uptake was studied.
Project description:Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells.
Project description:Development of melanoma brain metastasis is caused by an interaction between tumor cells and normal cells in the brain microenvironment. miRNAs delivered by exosomes derived from the tumor cells seem to prime the brain microenvironment, prior to extravasation of tumor cells into the brain. We investigated miRNA in exosomes extracted from normal (astrocytes, melanocytes) and metastatic melanoma cells (brain, skin and lymph node metastasis). We have discovered that miR-146a-5p is an important player in brain metastatic development: this miRNA was highly upregulated in exosomes from melanoma brain metastasis cells, compared to normal cells.
Project description:Over the last decades, exosomes have received increasing attention due to their involvement in numerous pathologies including cancer. Tumor-derived exosomes and exosomes derived from the tumor microenvironment are implicated in multiple mechanisms that support disease progression such as the escape of malignant cells from immunosurveillance, tumor cell growth, tumor angiogenesis, preparation of a pre-metastatic niche and remodeling of the extracellular matrix, thereby promoting dissemination and metastasis. Here, we performed protein expression phenotyping of exosomes derived from different invasive and proliferative melanoma cell lines (n=8) to provide a solid framework of gene expression programs, which - in a clinical setting - would be useful for prognosis and may also predict treatment response. Cell line characteristics have been published previously (Wenzina et al.,2020). Having identified a set of differentially expressed proteins in proliferative and invasive melanoma cell lines, we correlated them to the protein composition of plasma exosomes from melanoma patients pre and post immunotherapy treatment (n=7) as well as healthy controls (n=5).
