| Autor: |
Philip Chiu-Tsun Tang, Jeff Yat-Fai Chung, Jinyue Liao, Max Kam-Kwan Chan, Alex Siu-Wing Chan, Guangyao Cheng, Chunjie Li, Xiao-Ru Huang, Calvin Sze-Hang Ng, Eric W-F Lam, Dongmei Zhang, Yi-Ping Ho, Ka-Fai To, Kam-Tong Leung, Xiaohua Jiang, Ho Ko, Tin-Lap Lee, Hui-Yao Lan, Patrick Ming-Kuen Tang |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Science Advances. 8 |
| ISSN: |
2375-2548 |
| DOI: |
10.1126/sciadv.abn5535 |
| Popis: |
Tumor innervation is a common phenomenon with unknown mechanism. Here, we discovered a direct mechanism of tumor-associated macrophage (TAM) for promoting de novo neurogenesis via a subset showing neuronal phenotypes and pain receptor expression associated with cancer-driven nocifensive behaviors. This subset is rich in lung adenocarcinoma associated with poorer prognosis. By elucidating the transcriptome dynamics of TAM with single-cell resolution, we discovered a phenomenon “macrophage to neuron-like cell transition” (MNT) for directly promoting tumoral neurogenesis, evidenced by macrophage depletion and fate-mapping study in lung carcinoma models. Encouragingly, we detected neuronal phenotypes and activities of the bone marrow–derived MNT cells (MNTs) in vitro. Adoptive transfer of MNTs into NOD/SCID mice markedly enhanced their cancer-associated nocifensive behaviors. We identified macrophage-specific Smad3 as a pivotal regulator for promoting MNT at the genomic level; its disruption effectively blocked the tumor innervation and cancer-dependent nocifensive behaviors in vivo. Thus, MNT may represent a precision therapeutic target for cancer pain. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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