التفاصيل البيبلوغرافية
| العنوان: |
Adipose microenvironment promotes hypersialylation of ovarian cancer cells. |
| المؤلفون: |
Fox A, Leonard GD, Adzibolosu N, Wong T, Tedja R, Sharma S, Gogoi R, Morris R, Mor G, Fehl C, Alvero AB |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 May 15. Date of Electronic Publication: 2024 May 15. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Sialylation, the addition of negatively charged sialic acid sugars to terminal ends of glycans, is upregulated in most cancers. Hypersialylation supports multiple pro-tumor mechanisms such as enhanced migration and invasion, resistance to apoptosis and immune evasion. A current gap in knowledge is the lack of understanding on how the tumor microenvironment regulates cancer cell sialylation. The adipose niche is a main component of most peritoneal cancers' microenvironment. This includes ovarian cancer (OC), which causes most deaths from all gynecologic cancers. In this report, we demonstrate that the adipose microenvironment is a critical regulator of OC cell sialylation. In vitro adipose conditioning led to an increase in both ⍺2,3- and ⍺2,6-linked cell surface sialic acids in both human and mouse models of OC. Adipose-induced sialylation reprogramming was also observed in vivo from intra-peritoneal OC tumors seeded in the adipose-rich omentum. Mechanistically, we observed upregulation of at least three sialyltransferases, ST3GAL1, ST6GAL1 and ST3GALNAC3. Hypersialylated OC cells consistently formed intra-peritoneal tumors in both immune-competent mice and immune-compromised athymic nude mice. In contrast, hyposiaylated OC cells persistently formed tumors only in athymic nude mice demonstrating that sialylation impacts OC tumor formation in an immune dependent manner. To our knowledge, this is the first demonstration of the effect of adipose microenvironment on OC tumor sialylation. Our results set the stage for translational applications targeting sialic acid pathways in OC and other peritoneal cancers. |
| التعليقات: |
Update in: Front Oncol. 2024 Jul 22;14:1432333. doi: 10.3389/fonc.2024.1432333. (PMID: 39104719) |
| تواريخ الأحداث: |
Date Created: 20240527 Latest Revision: 20240812 |
| رمز التحديث: |
20240813 |
| مُعرف محوري في PubMed: |
PMC11118282 |
| DOI: |
10.1101/2024.05.13.593990 |
| PMID: |
38798490 |
| قاعدة البيانات: |
MEDLINE |
