Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes
Cancer cells tend to develop resistance to chemotherapy and enhance aggressiveness. A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic agents. Based on this strategy, induced tumor-suppressing cells (iTSCs) have been generated from tumor cells an...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-07-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304222002288 |
| _version_ | 1797802199868243968 |
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| author | Kexin Li Xun Sun Hudie Li Hailan Ma Meng Zhou Kazumasa Minami Keisuke Tamari Kazuhiko Ogawa Pankita H. Pandya M. Reza Saadatzadeh Melissa A. Kacena Karen E. Pollok Bai-Yan Li Hiroki Yokota |
| author_facet | Kexin Li Xun Sun Hudie Li Hailan Ma Meng Zhou Kazumasa Minami Keisuke Tamari Kazuhiko Ogawa Pankita H. Pandya M. Reza Saadatzadeh Melissa A. Kacena Karen E. Pollok Bai-Yan Li Hiroki Yokota |
| author_sort | Kexin Li |
| collection | DOAJ |
| description | Cancer cells tend to develop resistance to chemotherapy and enhance aggressiveness. A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic agents. Based on this strategy, induced tumor-suppressing cells (iTSCs) have been generated from tumor cells and mesenchymal stem cells. Here, we examined the possibility of generating iTSCs from lymphocytes by activating PKA signaling for suppressing the progression of osteosarcoma (OS). While lymphocyte-derived CM did not present anti-tumor capabilities, the activation of PKA converted them into iTSCs. Inhibiting PKA conversely generated tumor-promotive secretomes. In a mouse model, PKA-activated CM suppressed tumor-induced bone destruction. Proteomics analysis revealed that moesin (MSN) and calreticulin (Calr), which are highly expressed intracellular proteins in many cancers, were enriched in PKA-activated CM, and they acted as extracellular tumor suppressors through CD44, CD47, and CD91. The study presented a unique option for cancer treatment by generating iTSCs that secret tumor-suppressive proteins such as MSN and Calr. We envision that identifying these tumor suppressors and predicting their binding partners such as CD44, which is an FDA-approved oncogenic target to be inhibited, may contribute to developing targeted protein therapy. |
| first_indexed | 2024-03-13T05:02:07Z |
| format | Article |
| id | doaj.art-d040b7e31d9e44aebea1c63c1d145289 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-13T05:02:07Z |
| publishDate | 2023-07-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-d040b7e31d9e44aebea1c63c1d1452892023-06-17T05:19:01ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-07-0110416411656Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomesKexin Li0Xun Sun1Hudie Li2Hailan Ma3Meng Zhou4Kazumasa Minami5Keisuke Tamari6Kazuhiko Ogawa7Pankita H. Pandya8M. Reza Saadatzadeh9Melissa A. Kacena10Karen E. Pollok11Bai-Yan Li12Hiroki Yokota13Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanSimon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USASimon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USASimon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USASimon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China; Corresponding author.Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA; Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Corresponding author. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.Cancer cells tend to develop resistance to chemotherapy and enhance aggressiveness. A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic agents. Based on this strategy, induced tumor-suppressing cells (iTSCs) have been generated from tumor cells and mesenchymal stem cells. Here, we examined the possibility of generating iTSCs from lymphocytes by activating PKA signaling for suppressing the progression of osteosarcoma (OS). While lymphocyte-derived CM did not present anti-tumor capabilities, the activation of PKA converted them into iTSCs. Inhibiting PKA conversely generated tumor-promotive secretomes. In a mouse model, PKA-activated CM suppressed tumor-induced bone destruction. Proteomics analysis revealed that moesin (MSN) and calreticulin (Calr), which are highly expressed intracellular proteins in many cancers, were enriched in PKA-activated CM, and they acted as extracellular tumor suppressors through CD44, CD47, and CD91. The study presented a unique option for cancer treatment by generating iTSCs that secret tumor-suppressive proteins such as MSN and Calr. We envision that identifying these tumor suppressors and predicting their binding partners such as CD44, which is an FDA-approved oncogenic target to be inhibited, may contribute to developing targeted protein therapy.http://www.sciencedirect.com/science/article/pii/S2352304222002288CalreticulinLymphocytesMoesinOsteosarcomaPKAProteome |
| spellingShingle | Kexin Li Xun Sun Hudie Li Hailan Ma Meng Zhou Kazumasa Minami Keisuke Tamari Kazuhiko Ogawa Pankita H. Pandya M. Reza Saadatzadeh Melissa A. Kacena Karen E. Pollok Bai-Yan Li Hiroki Yokota Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes Genes and Diseases Calreticulin Lymphocytes Moesin Osteosarcoma PKA Proteome |
| title | Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes |
| title_full | Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes |
| title_fullStr | Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes |
| title_full_unstemmed | Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes |
| title_short | Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes |
| title_sort | suppression of osteosarcoma progression by engineered lymphocyte derived proteomes |
| topic | Calreticulin Lymphocytes Moesin Osteosarcoma PKA Proteome |
| url | http://www.sciencedirect.com/science/article/pii/S2352304222002288 |
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