한빛사 논문
Dong-Sic Choi†§, Jae-Min Lee†§, Gun Wook Park‡, Hyeon-Woo Lim†, Joo Young Bang⊥, Yoon-Keun Kim†, Kyung-Hoon Kwon‡, Ho Jeong Kwon∥, Kwang Pyo Kim⊥ and Yong Song Gho*†
†Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea, ‡Mass Spectrometer Development Team, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea, ∥Department of Biotechnology, College of Engineering, Yonsei University, Seoul 120-749, Republic of Korea, and ⊥Institute of Biomedical Science and Technology, Department of Molecular Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea
§ These authors contributed equally to this work.
* To whom correspondence should be addressed.
Abstract
Microvesicles (MV) are membrane vesicles secreted from the plasma and endosomal membrane compartment by various cell types such as hematopoietic, epithelial, and tumor cells. Actively growing tumor cells shed MV, and the rate of shedding increases in malignant tumors. Although recent progress in this area has revealed that tumor-derived MV play multiple roles in tumor growth and metastasis via immune escape, tumor invasion, and angiogenesis, the mechanism of vesicle formation and the biological roles of tumor-derived MV are not understood. Here, we report the first global proteomic analysis of highly purified MV from human colorectal cancer cells. Using 1D SDS gel electrophoresis and nano-LC-MS/MS analyses, we identified a total of 547 microvesicular proteins from three independent experiments with high confidence; 416 proteins were identified at least in two trials, including 181 as yet unreported proteins. We identified 49 proteins involved in the biogenesis of MV, including annexins, ADP-ribosylation factors, and Rab proteins. We also identified 28 proteins that may function in tumorigenesis via promotion of migration, invasion, and growth of tumor cells, immune modulation, metastasis, and angiogenesis. Taken together with previously reported results, our observations suggest that tumor-derived MV may act as communicasomes, that is, extracellular organelles that play diverse roles in intercellular communication. This information will help elucidate the biogenesis and functions of tumor-derived MV, and aid in the development of effective vaccines for various cancers, including colorectal cancer.
Keywords: colorectal cancer; communicasomes; exosomes; HT29; microparticles; microvesicles; proteomics; tolerosomes
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