Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia
Relieving hypoxia in the tumor microenvironment (TME) promotes innate and adaptive immunity. Our previous research demonstrated that reoxygenation of the TME promotes the phagocytosis and tumor-killing functions of tumor-associated macrophages (TAMs) by upregulating pyruvate carboxylase (PCB). Howev...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2025-01-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2025011 |
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| author | Shu Yuxin Zhou Linmin Qian Jinqin Zhu Wei-Guo |
| author_facet | Shu Yuxin Zhou Linmin Qian Jinqin Zhu Wei-Guo |
| author_sort | Shu Yuxin |
| collection | DOAJ |
| description | Relieving hypoxia in the tumor microenvironment (TME) promotes innate and adaptive immunity. Our previous research demonstrated that reoxygenation of the TME promotes the phagocytosis and tumor-killing functions of tumor-associated macrophages (TAMs) by upregulating pyruvate carboxylase (PCB). However, the mechanism remains obscure. In the present study, we find that versican derived from melanoma cells binds to TLR2 and activates the downstream transcription factor RelB, which transcribes PCB under normoxia. Blocking the versican-TLR2-MyD88-RelB axis not only reverses the upregulation of PCB in TAMs but also hinders the clearance of tumor cells by TAMs. Our work suggests a pathway that modulates the functions of TAMs under normoxia, which could be harnessed for strengthening anti-tumor immunity. |
| format | Article |
| id | doaj-art-e2c83d1b21b34cc4b3b6db28e0177ce2 |
| institution | Kabale University |
| issn | 1672-9145 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-e2c83d1b21b34cc4b3b6db28e0177ce22025-08-20T03:30:03ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452025-01-015787187810.3724/abbs.202501120d259ccMelanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxiaShu Yuxin0Zhou Linmin1Qian Jinqin2Zhu Wei-Guo3["International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen 518060, China","School of Basic Medical Sciences, Wannan Medical College, Wuhu 241002, China"]["School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen 518055, China"]["Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center of China, Beijing 100034, China"]["International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen 518060, China","School of Basic Medical Sciences, Wannan Medical College, Wuhu 241002, China"]Relieving hypoxia in the tumor microenvironment (TME) promotes innate and adaptive immunity. Our previous research demonstrated that reoxygenation of the TME promotes the phagocytosis and tumor-killing functions of tumor-associated macrophages (TAMs) by upregulating pyruvate carboxylase (PCB). However, the mechanism remains obscure. In the present study, we find that versican derived from melanoma cells binds to TLR2 and activates the downstream transcription factor RelB, which transcribes PCB under normoxia. Blocking the versican-TLR2-MyD88-RelB axis not only reverses the upregulation of PCB in TAMs but also hinders the clearance of tumor cells by TAMs. Our work suggests a pathway that modulates the functions of TAMs under normoxia, which could be harnessed for strengthening anti-tumor immunity.https://www.sciengine.com/doi/10.3724/abbs.2025011pyruvate carboxylasephagocytosisRelBtumor-associated macrophagesversican |
| spellingShingle | Shu Yuxin Zhou Linmin Qian Jinqin Zhu Wei-Guo Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia Acta Biochimica et Biophysica Sinica pyruvate carboxylase phagocytosis RelB tumor-associated macrophages versican |
| title | Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia |
| title_full | Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia |
| title_fullStr | Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia |
| title_full_unstemmed | Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia |
| title_short | Melanoma-derived versican reactivates tumor-associated macrophages by upregulating pyruvate carboxylase through TLR2-MyD88-RelB axis under normoxia |
| title_sort | melanoma derived versican reactivates tumor associated macrophages by upregulating pyruvate carboxylase through tlr2 myd88 relb axis under normoxia |
| topic | pyruvate carboxylase phagocytosis RelB tumor-associated macrophages versican |
| url | https://www.sciengine.com/doi/10.3724/abbs.2025011 |
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