| First Author | Tang PC | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 40 | Pages | eabn5535 |
| PubMed ID | 36206343 | Mgi Jnum | J:330940 |
| Mgi Id | MGI:7379721 | Doi | 10.1126/sciadv.abn5535 |
| Citation | Tang PC, et al. (2022) Single-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain. Sci Adv 8(40):eabn5535 |
| abstractText | 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. |
