Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.
Br J Cancer
; 130(9): 1463-1476, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38438589
ABSTRACT
BACKGROUND:
Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking.METHODS:
We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function.RESULTS:
TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids.CONCLUSION:
These findings suggest inhibiting Gal3 may benefit USC patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Uterinas
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Proteínas Sanguíneas
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Cistadenocarcinoma Seroso
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Galectina 3
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2024
Tipo de documento:
Article