| First Author | Gong Z | Year | 2022 |
| Journal | Cell Metab | Volume | 34 |
| Issue | 12 | Pages | 1960-1976.e9 |
| PubMed ID | 36476935 | Mgi Jnum | J:332914 |
| Mgi Id | MGI:7410724 | Doi | 10.1016/j.cmet.2022.11.003 |
| Citation | Gong Z, et al. (2022) Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells. Cell Metab 34(12):1960-1976.e9 |
| abstractText | While the distant organ environment is known to support metastasis of primary tumors, its metabolic roles in this process remain underdetermined. Here, in breast cancer models, we found lung-resident mesenchymal cells (MCs) accumulating neutral lipids at the pre-metastatic stage. This was partially mediated by interleukin-1beta (IL-1beta)-induced hypoxia-inducible lipid droplet-associated (HILPDA) that subsequently represses adipose triglyceride lipase (ATGL) activity in lung MCs. MC-specific ablation of the ATGL or HILPDA genes in mice reinforced and reduced lung metastasis of breast cancer respectively, suggesting a metastasis-promoting effect of lipid-laden MCs. Mechanistically, lipid-laden MCs transported their lipids to tumor cells and natural killer (NK) cells via exosome-like vesicles, leading to heightened tumor cell survival and proliferation and NK cell dysfunction. Blockage of IL-1beta, which was effective singly, improved the efficacy of adoptive NK cell immunotherapy in mitigating lung metastasis. Collectively, lung MCs metabolically regulate tumor cells and anti-tumor immunity to facilitate breast cancer lung metastasis. |
