New treatment strategies for uterine sarcoma using secreted frizzled‑related proteins
Tomohiro Kagawa1, Ayuka Mineda1, Tomotaka Nakagawa1
1Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
Abstract:
Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.
Insights
Secreted frizzled-related proteins (SFRPs) suppress Wnt signaling in cancer. SFRP4 was found at lower levels in uterine sarcoma, where it inhibited cell viability and migration, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Secreted frizzled-related proteins (SFRPs) are antagonists of the Wnt signaling pathway, implicated in various cancers.
- The role of SFRPs, particularly SFRP4, in the pathogenesis and progression of uterine sarcoma remains underexplored.
Purpose of the Study:
- To investigate the expression levels of SFRP4 in uterine sarcoma tissues.
- To evaluate the functional effects of SFRP4 on uterine leiomyosarcoma cell behavior, including viability, migration, and adhesion.
Main Methods:
- Immunohistochemical staining was used to assess SFRP4 expression in uterine smooth muscle, fibroid, and leiomyosarcoma tissues.
- In vitro assays (WST-1, cell migration, cell adhesion) were performed on uterine leiomyosarcoma SKN cells treated with SFRP4.
Main Results:
- SFRP4 expression was significantly lower in uterine leiomyosarcoma tissues compared to normal smooth muscle and uterine fibroid tissues.
- SFRP4 administration suppressed cell viability and migration of uterine leiomyosarcoma cells.
- SFRP4 treatment enhanced the adhesion ability of uterine leiomyosarcoma cells.
Conclusions:
- SFRP4 exhibits tumor-suppressive properties in uterine leiomyosarcoma by reducing cell viability and migration while increasing cell adhesion.
- These findings highlight SFRP4 as a potential novel therapeutic target for uterine sarcoma.
