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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/83768 |
| _version_ | 1827985853505339392 |
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| author | Kexin Li Qingji Huo Nathan H Dimmitt Guofan Qu Junjie Bao Pankita H Pandya M Reza Saadatzadeh Khadijeh Bijangi-Vishehsaraei Melissa A Kacena Karen E Pollok Chien-Chi Lin Bai-Yan Li Hiroki Yokota |
| author_facet | Kexin Li Qingji Huo Nathan H Dimmitt Guofan Qu Junjie Bao Pankita H Pandya M Reza Saadatzadeh Khadijeh Bijangi-Vishehsaraei Melissa A Kacena Karen E Pollok Chien-Chi Lin Bai-Yan Li Hiroki Yokota |
| author_sort | Kexin Li |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T23:22:12Z |
| format | Article |
| id | doaj.art-ba8234a336c14e4ea67c0a581db5fd95 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T23:22:12Z |
| publishDate | 2023-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ba8234a336c14e4ea67c0a581db5fd952023-03-21T16:03:38ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.83768Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteinsKexin Li0Qingji Huo1https://orcid.org/0000-0003-0438-6812Nathan H Dimmitt2Guofan Qu3Junjie Bao4Pankita H Pandya5M Reza Saadatzadeh6Khadijeh Bijangi-Vishehsaraei7https://orcid.org/0009-0009-2522-8806Melissa A Kacena8https://orcid.org/0000-0001-7293-0088Karen E Pollok9Chien-Chi Lin10https://orcid.org/0000-0002-4175-8796Bai-Yan Li11Hiroki Yokota12https://orcid.org/0000-0002-7881-8959Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United StatesDepartment of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United StatesDepartment of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United StatesDepartment of Orthopedic Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Orthopedic Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaIndiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, United StatesIndiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Pediatric Hematology and Oncology, Indiana University School of Medicine, Indianapolis, United StatesIndiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, United States; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, United StatesIndiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United States; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, ChinaDepartment of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United States; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, United StatesOsteosarcoma (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.https://elifesciences.org/articles/83768osteosarcomaMSCproteomecalreticulinCD47PCOLCE |
| spellingShingle | Kexin Li Qingji Huo Nathan H Dimmitt Guofan Qu Junjie Bao Pankita H Pandya M Reza Saadatzadeh Khadijeh Bijangi-Vishehsaraei Melissa A Kacena Karen E Pollok Chien-Chi Lin Bai-Yan Li Hiroki Yokota Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins eLife osteosarcoma MSC proteome calreticulin CD47 PCOLCE |
| 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 | osteosarcoma MSC proteome calreticulin CD47 PCOLCE |
| url | https://elifesciences.org/articles/83768 |
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