Lack of sensitivity and specificity of current tumor markers has intensified research efforts to find new biomarkers. The identification of potential tumor markers in human body fluids is hampered by large variability and complexity of both control and patient samples, laborious biochemical analyses, and the fact that the identified proteins are unlikely produced by the diseased cells but are due to secondary body defense mechanisms. In a new approach presented here, we eliminate these problems by performing proteomic analysis in a prostate cancer xenograft model in which human prostate cancer cells form a tumor in an immune-incompetent nude mouse. Using this concept, proteins present in mouse serum that can be identified as human will, by definition, originate from the human prostate cancer xenograft and might have potential diagnostic and prognostic value. Using one-dimensional gel electrophoresis, liquid chromatography, and mass spectrometry, we identified tumor-derived human nm23/nucleoside-diphosphate kinase (NME) in the serum of a nude mouse bearing the androgen-independent human prostate cancer xenograft PC339. NME is known to be involved in the metastatic potential of several tumor cells, including prostate cancer cells. Furthermore we identified six human enzymes involved in glycolysis (fructose-bisphosphate aldolase A, triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, alpha enolase, and lactate dehydrogenases A and B) in the serum of the tumor-bearing mice. The presence of human NME and glyceraldehyde-3-phosphate dehydrogenase in the serum of PC339-bearing mice was confirmed by Western blotting. Although the putative usefulness of these proteins in predicting prognosis of prostate cancer remains to be determined, the present data illustrate that our approach is a promising tool for the focused discovery of new prostate cancer biomarkers.
"An obvious problem with this approach is that in a discovery setting, the protein or RNA marker of interest is not known. However, recent findings have revealed that small tissuederived vesicles, the so-called exosomes, are present in serum and urine and contain a wide range of proteins and RNAs   that represent their tissue origin. These vesicles also express tissue-specific transmembrane proteins that can be used for specific isolation of the vesicles from the complex fluids. "
[Show abstract][Hide abstract] ABSTRACT: Although progress has been made with regard to types of markers (protein, DNA, RNA, and metabolites) and implementation of improved technologies (mass spectrometry, arrays, and deep sequencing), the discovery of novel biomarkers for prostate cancer (PCa) in complex fluids, such as serum and urine, remains a challenge. Meanwhile, recent studies have reported that many cancer-derived proteins and RNAs are secreted through small vesicles known as exosomes.
This narrative review describes recent progress in exosome research, focusing on the potential role of exosomes as novel biomarkers for PCa. The purpose of this review is to acquaint clinicians and researchers in the field of urology with the potential role of exosomes as biomarker treasure chests and with their clinical value.
Medline and Embase entries between 1966 and September 2010 were searched using the keywords exosomes, microvesicles, prostasomes, biomarkers, prostate cancer, and urology. Leading publications and articles constructively contributing to exosome research were selected for this review.
Exosomes are small vesicles (50-100 nm) secreted by almost all tissues; they represent their tissue origin. Purification of prostate- and PCa-derived exosomes will allow us to profile exosomes, providing a promising source of protein and RNA biomarkers for PCa. This profiling will contribute to the discovery of novel markers for the early diagnosis and reliable prognosis of PCa.
Although the initial results are promising, further investigations are required to assess the clinical value of these exosomes in PCa.
European Urology 12/2010; 59(5):823-31. DOI:10.1016/j.eururo.2010.12.031 · 13.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prognosis of malignant neuroendocrine tumors of the lung is known to be very poor. Aiming to identify new markers of pulmonary neuroendocrine tumors in early stages and also differential diagnostic markers between large cell neuroendocrine carcinoma and small cell lung cancer, we comprehensively analyzed peptides which were secreted into conditioned medium by LCN1, a large cell neuroendocrine carcinoma cell line. Specific peaks in conditioned medium but not in used medium alone were detected using matrix-associated laser desorption/ionization time of flight mass spectrometry. Two peptide fragments of 40 and 19 amino acid residues were identified by matrix-associated laser desorption/ionization time of flight mass spectrometry. These two fragments were demonstrated to be parts of VGF nerve growth factor inducible (VGF), which is usually expressed in nerve cells or neuroendocrine cells. RT-PCR analysis of lung cancer cell lines showed that VGF mRNA was expressed only in neuroendocrine carcinoma-derived cells. Our data suggest that VGF can be used as a novel serological diagnostic marker of pulmonary neuroendocrine tumors.
The International journal of biological markers 24(4):282-5. · 1.37 Impact Factor
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