A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer
Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/944 |
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| author | Ting Deng Yibo Hou Gaoyang Lin Chunyan Feng Kewei Liu Wenke Chen Wei Wei Laiqiang Huang Xiaoyong Dai |
| author_facet | Ting Deng Yibo Hou Gaoyang Lin Chunyan Feng Kewei Liu Wenke Chen Wei Wei Laiqiang Huang Xiaoyong Dai |
| author_sort | Ting Deng |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8<sup>+</sup> T and NKT (natural killer T) cells and inhibiting CD25<sup>+</sup> Foxp3<sup>+</sup> Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/β-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment. |
| first_indexed | 2024-03-11T06:02:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:02:17Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7a154ce7949e4e60810d9f844e071eeb2023-11-17T13:16:36ZengMDPI AGPharmaceutics1999-49232023-03-0115394410.3390/pharmaceutics15030944A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal CancerTing Deng0Yibo Hou1Gaoyang Lin2Chunyan Feng3Kewei Liu4Wenke Chen5Wei Wei6Laiqiang Huang7Xiaoyong Dai8Precision Medicine and Healthcare Research Center, Center for Biotechnology and Biomedicine, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, State Key Laboratory of Health Sciences and Technology, Tsinghua-Berkeley Shenzhen Institute (TBSI), Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaPrecision Medicine and Healthcare Research Center, Center for Biotechnology and Biomedicine, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, State Key Laboratory of Health Sciences and Technology, Tsinghua-Berkeley Shenzhen Institute (TBSI), Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaPrecision Medicine and Healthcare Research Center, Center for Biotechnology and Biomedicine, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, State Key Laboratory of Health Sciences and Technology, Tsinghua-Berkeley Shenzhen Institute (TBSI), Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaPrecision Medicine and Healthcare Research Center, Center for Biotechnology and Biomedicine, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, State Key Laboratory of Health Sciences and Technology, Tsinghua-Berkeley Shenzhen Institute (TBSI), Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaPrecision Medicine and Healthcare Research Center, Center for Biotechnology and Biomedicine, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, State Key Laboratory of Health Sciences and Technology, Tsinghua-Berkeley Shenzhen Institute (TBSI), Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaPeking University Shenzhen Hospital, Shenzhen 518036, ChinaPeking University Shenzhen Hospital, Shenzhen 518036, ChinaPrecision Medicine and Healthcare Research Center, Center for Biotechnology and Biomedicine, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, State Key Laboratory of Health Sciences and Technology, Tsinghua-Berkeley Shenzhen Institute (TBSI), Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaPrecision Medicine and Healthcare Research Center, Center for Biotechnology and Biomedicine, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, State Key Laboratory of Health Sciences and Technology, Tsinghua-Berkeley Shenzhen Institute (TBSI), Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaColorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8<sup>+</sup> T and NKT (natural killer T) cells and inhibiting CD25<sup>+</sup> Foxp3<sup>+</sup> Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/β-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment.https://www.mdpi.com/1999-4923/15/3/944fibromodulincolorectal cancermetastasistumor microenvironmentAKT signaling pathwayWnt/β-catenin signaling pathway |
| spellingShingle | Ting Deng Yibo Hou Gaoyang Lin Chunyan Feng Kewei Liu Wenke Chen Wei Wei Laiqiang Huang Xiaoyong Dai A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer Pharmaceutics fibromodulin colorectal cancer metastasis tumor microenvironment AKT signaling pathway Wnt/β-catenin signaling pathway |
| title | A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer |
| title_full | A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer |
| title_fullStr | A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer |
| title_full_unstemmed | A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer |
| title_short | A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer |
| title_sort | novel fibromodulin antagonist peptide rp4 exerts antitumor effects on colorectal cancer |
| topic | fibromodulin colorectal cancer metastasis tumor microenvironment AKT signaling pathway Wnt/β-catenin signaling pathway |
| url | https://www.mdpi.com/1999-4923/15/3/944 |
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