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Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes

Tumor cells produce and utilize exosomes to promote tumor growth and metastasis. Tumor-cell-derived exosomes deliver cargos that partially mimic the contents of the parent cell to nearby or distant normal or abnormal cells, thereby reprogramming the recipient cells to support tumor progression. Mech...

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Autores principales: Purushothaman, Anurag, Bandari, Shyam K., Chandrashekar, Darshan S., Jones, Richard J., Lee, Hans C., Weber, Donna M., Orlowski, Robert Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650294/
https://www.ncbi.nlm.nih.gov/pubmed/29088739
http://dx.doi.org/10.18632/oncotarget.20564
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author Purushothaman, Anurag
Bandari, Shyam K.
Chandrashekar, Darshan S.
Jones, Richard J.
Lee, Hans C.
Weber, Donna M.
Orlowski, Robert Z.
author_facet Purushothaman, Anurag
Bandari, Shyam K.
Chandrashekar, Darshan S.
Jones, Richard J.
Lee, Hans C.
Weber, Donna M.
Orlowski, Robert Z.
author_sort Purushothaman, Anurag
collection PubMed
description Tumor cells produce and utilize exosomes to promote tumor growth and metastasis. Tumor-cell-derived exosomes deliver cargos that partially mimic the contents of the parent cell to nearby or distant normal or abnormal cells, thereby reprogramming the recipient cells to support tumor progression. Mechanisms by which tumor-derived exosomes subserve the tumor are under intense investigation. Here we demonstrate a critical role of the chondroitin sulfate proteoglycan serglycin in regulating the protein cargo and functions of myeloma cell-derived exosomes. Previous studies have shown that serglycin, the only known intracellular proteoglycan, functions mainly in the storage of basically charged components within the intracellular granules/vesicles via serglycin’s densely clustered, negatively charged glycosaminoglycan chains. Here we demonstrate that serglycin plays a critical role in the protein cargo loading of tumor-derived exosomes. Serglycin was detected in exosomes derived from cell culture supernatants of human myeloma cell lines and serum of myeloma patients. Mass spectrometry analysis of exosomal proteins identified significantly fewer protein components within exosomes derived from serglycin-knockdown myeloma cells than within exosomes from control cells. On gene ontology analysis, exosomes derived from serglycin-knockdown cells, but not from control cells, lacked many proteins that are required for mediating different cellular processes. In functional assays, exosomes from serglycin-knockdown cells failed to induce an invasive phenotype in myeloma cells and failed to promote migration of macrophages. These findings reveal that serglycin plays an important role in maintaining the protein cargo in tumor-derived exosomes and suggest that targeting serglycin may temper the influence of these exosomes on cancer progression.
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spelling pubmed-56502942017-10-30 Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes Purushothaman, Anurag Bandari, Shyam K. Chandrashekar, Darshan S. Jones, Richard J. Lee, Hans C. Weber, Donna M. Orlowski, Robert Z. Oncotarget Research Paper Tumor cells produce and utilize exosomes to promote tumor growth and metastasis. Tumor-cell-derived exosomes deliver cargos that partially mimic the contents of the parent cell to nearby or distant normal or abnormal cells, thereby reprogramming the recipient cells to support tumor progression. Mechanisms by which tumor-derived exosomes subserve the tumor are under intense investigation. Here we demonstrate a critical role of the chondroitin sulfate proteoglycan serglycin in regulating the protein cargo and functions of myeloma cell-derived exosomes. Previous studies have shown that serglycin, the only known intracellular proteoglycan, functions mainly in the storage of basically charged components within the intracellular granules/vesicles via serglycin’s densely clustered, negatively charged glycosaminoglycan chains. Here we demonstrate that serglycin plays a critical role in the protein cargo loading of tumor-derived exosomes. Serglycin was detected in exosomes derived from cell culture supernatants of human myeloma cell lines and serum of myeloma patients. Mass spectrometry analysis of exosomal proteins identified significantly fewer protein components within exosomes derived from serglycin-knockdown myeloma cells than within exosomes from control cells. On gene ontology analysis, exosomes derived from serglycin-knockdown cells, but not from control cells, lacked many proteins that are required for mediating different cellular processes. In functional assays, exosomes from serglycin-knockdown cells failed to induce an invasive phenotype in myeloma cells and failed to promote migration of macrophages. These findings reveal that serglycin plays an important role in maintaining the protein cargo in tumor-derived exosomes and suggest that targeting serglycin may temper the influence of these exosomes on cancer progression. Impact Journals LLC 2017-08-27 /pmc/articles/PMC5650294/ /pubmed/29088739 http://dx.doi.org/10.18632/oncotarget.20564 Text en Copyright: © 2017 Purushothaman et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Purushothaman, Anurag
Bandari, Shyam K.
Chandrashekar, Darshan S.
Jones, Richard J.
Lee, Hans C.
Weber, Donna M.
Orlowski, Robert Z.
Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes
title Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes
title_full Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes
title_fullStr Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes
title_full_unstemmed Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes
title_short Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes
title_sort chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650294/
https://www.ncbi.nlm.nih.gov/pubmed/29088739
http://dx.doi.org/10.18632/oncotarget.20564
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