دورية أكاديمية
Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis.
العنوان: | Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis. |
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المؤلفون: | Niu S; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Cheng K; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Jia L; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Liang J; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Mu L; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Wang Y; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Yang X; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Yang C; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Zhang Y; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Wang C; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China., Huang L; Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Wang H; Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Zhang S; Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. zhangshuang0122@gmail.com., Zhang H; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. huazhang@cau.edu.cn. |
المصدر: | Cell death and differentiation [Cell Death Differ] 2023 May; Vol. 30 (5), pp. 1235-1246. Date of Electronic Publication: 2023 Feb 23. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9437445 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5403 (Electronic) Linking ISSN: 13509047 NLM ISO Abbreviation: Cell Death Differ Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2003->: London : Nature Publishing Group Original Publication: London : Edward Arnold, c1994- |
مواضيع طبية MeSH: | Granulosa Cell Tumor*/genetics , Granulosa Cell Tumor*/drug therapy , Granulosa Cell Tumor*/pathology , Ovarian Neoplasms*/genetics , Ovarian Neoplasms*/pathology, Mice ; Female ; Animals ; Humans ; CD47 Antigen/genetics ; Granulosa Cells ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Cell Transformation, Neoplastic/pathology ; Mice, Knockout |
مستخلص: | 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. (© 2023. The Author(s).) |
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المشرفين على المادة: | 0 (CD47 Antigen) |
تواريخ الأحداث: | Date Created: 20230224 Date Completed: 20230504 Latest Revision: 20230505 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC10154338 |
DOI: | 10.1038/s41418-023-01132-1 |
PMID: | 36823373 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-5403 |
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DOI: | 10.1038/s41418-023-01132-1 |