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: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.
