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Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins
Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned me...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030111/ https://www.ncbi.nlm.nih.gov/pubmed/36943734 http://dx.doi.org/10.7554/eLife.83768 |
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author | Li, Kexin Huo, Qingji Dimmitt, Nathan H Qu, Guofan Bao, Junjie Pandya, Pankita H Saadatzadeh, M Reza Bijangi-Vishehsaraei, Khadijeh Kacena, Melissa A Pollok, Karen E Lin, Chien-Chi Li, Bai-Yan Yokota, Hiroki |
author_facet | Li, Kexin Huo, Qingji Dimmitt, Nathan H Qu, Guofan Bao, Junjie Pandya, Pankita H Saadatzadeh, M Reza Bijangi-Vishehsaraei, Khadijeh Kacena, Melissa A Pollok, Karen E Lin, Chien-Chi Li, Bai-Yan Yokota, Hiroki |
author_sort | Li, Kexin |
collection | PubMed |
description | Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with cisplatin. CM was enriched with proteins such as calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of CALR transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein, a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS. |
format | Online Article Text |
id | pubmed-10030111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-100301112023-03-22 Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins Li, Kexin Huo, Qingji Dimmitt, Nathan H Qu, Guofan Bao, Junjie Pandya, Pankita H Saadatzadeh, M Reza Bijangi-Vishehsaraei, Khadijeh Kacena, Melissa A Pollok, Karen E Lin, Chien-Chi Li, Bai-Yan Yokota, Hiroki eLife Cancer Biology Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with cisplatin. CM was enriched with proteins such as calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of CALR transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein, a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS. eLife Sciences Publications, Ltd 2023-03-21 /pmc/articles/PMC10030111/ /pubmed/36943734 http://dx.doi.org/10.7554/eLife.83768 Text en © 2023, Li et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cancer Biology Li, Kexin Huo, Qingji Dimmitt, Nathan H Qu, Guofan Bao, Junjie Pandya, Pankita H Saadatzadeh, M Reza Bijangi-Vishehsaraei, Khadijeh Kacena, Melissa A Pollok, Karen E Lin, Chien-Chi Li, Bai-Yan Yokota, Hiroki Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins |
title | Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins |
title_full | Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins |
title_fullStr | Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins |
title_full_unstemmed | Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins |
title_short | Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins |
title_sort | osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030111/ https://www.ncbi.nlm.nih.gov/pubmed/36943734 http://dx.doi.org/10.7554/eLife.83768 |
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