| First Author | Niu S | Year | 2023 |
| Journal | Cell Death Differ | Volume | 30 |
| Issue | 5 | Pages | 1235-1246 |
| PubMed ID | 36823373 | Mgi Jnum | J:335438 |
| Mgi Id | MGI:7470648 | Doi | 10.1038/s41418-023-01132-1 |
| Citation | Niu S, et al. (2023) Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis. Cell Death Differ 30(5):1235-1246 |
| abstractText | Ovarian granulosa cell tumors (GCTs) originate from granulosa cells (GCs) and represent the most common sex cord-stromal tumor in humans. However, the developmental regulations and molecular mechanisms underlying their etiology are largely unknown. In the current study, we combined a multi-fluorescent reporter mouse model with a conditional knockout mouse model, in which the tumor suppressor genes Pten and p27 were deleted in GCs, to perform cell lineage tracing of mutant GCs. We found that only 30% of ovaries with substantial mutant GCs developed into GCTs that derived from a single mutant GC. In-depth molecular analysis of the process of tumorigenesis demonstrated that up-regulation of immune evasion genes Cd24a and Cd47 led, in part, to the transition of mutant GCs to GCTs. Therefore, treatment with the Cd47 inhibitor RRX-001 was tested and found to efficiently suppress the growth of GCTs in vivo. Together, our study has revealed an immune evasion mechanism via CD24/CD47 upregulation to GCT formation, shedding light on the future potential clinical therapies for GCTs. |
