Abstract
Prostate cancer is the leading type of cancer diagnosed in men. In 2010, ~217,730 new cases of prostate cancer were reported in the United States. Prompt diagnosis of the disease can substantially improve its clinical outcome. Improving capability for early detection, as well as developing new therapeutic targets in advanced disease are research priorities that will ultimately lead to better patient survival. Eukaryotic cells secrete proteins via distinct regulated mechanisms which are either ER/Golgi dependent or microvesicle mediated. The release of microvesicles has been shown to provide a novel mechanism for intercellular communication. Exosomes are nanometer sized cup-shaped membrane vesicles which are secreted from normal and cancerous cells. They are present in various biological fluids and are rich in characteristic proteins. Exosomes may thus have potential both in facilitating early diagnosis via less invasive procedures or be candidates for novel therapeutic approaches for castration resistance prostate cancer. Because exosomes have been shown previously to have a role in cell-cell communication in the local tumor microenvironment, conferring activation of numerous survival mechanisms, we characterized constitutive lipids, cholesterol and proteins from exosomes derived from six prostate cell lines and tracked their uptake in both cancerous and benign prostate cell lines respectively. Our comprehensive proteomic and lipidomic analysis of prostate derived exosomes could provide insight for future work on both biomarker and therapeutic targets for the treatment of prostate cancer.
Highlights
Prostate cancer (PCa)1 is the leading type of cancer diagnosed in men
All cells produce and release exosomes, which are often found in different body fluids such as plasma [8], serum [9, 10] malignant ascites
HSP90, a stress marker often associated with cancer [35], was not enriched in either cell lysate or exosomes from the benign epithelial prostate cell line RWPE-1 substantial amounts of HSP90 were observed in the PCa cell lines
Summary
Prostate cancer (PCa) is the leading type of cancer diagnosed in men. The American Cancer Society reported. All cells produce and release exosomes, which are often found in different body fluids such as plasma [8], serum [9, 10] malignant ascites Accumulating evidence suggests that induction of intracellular calcium [22,23,24,25], overexpression of Rab or citron kinase [26] as well as a reduction in membrane cholesterol, or inhibition of cholesterol biosynthesis [27], could stimulate the release of exosomes into the microenvironment
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