KEY TAKEAWAYS
- The study aimed to investigate the role and mechanism of SLC3A2 in BLCA onset and progression.
- Researchers noticed that interference with SLC3A2 inhibited BLCA cell growth and macrophage polarization by promoting ferroptosis, suggesting a potential therapeutic target.
Solute carrier family 3 member 2 (SLC3A2) is frequently overexpressed in numerous cancer types, including bladder cancer (BLCA). Despite its known association with cancer, the precise role and mechanisms of SLC3A2 in BLCA initiation and progression remain elusive.
Peishan Wu and the team aimed to assess the impact of SLC3A2 on BLCA development and progression.
They performed an inclusive analysis by constructing and transfecting an interfering plasmid for SLC3A2 into BLCA cells. Cell proliferation, invasion, and migration abilities were evaluated to assess the impact of SLC3A2 silencing on BLCA cell growth. M1 and M2 macrophage polarization markers were detected to evaluate macrophage polarization. The levels of reactive oxygen species (ROS), lipid peroxidation, and Fe2+, as well as the expression of ferroptosis-related proteins, were measured to assess the occurrence of ferroptosis. Ferroptosis inhibitors were utilized to verify the mechanism.
SLC3A2 exhibited high expression levels in BLCA cell lines. Interference with SLC3A2 resulted in decreased proliferation, invasion, and migration of BLCA cells. This interference led to an increase in M1 macrophage marker expression and a decrease in M2 macrophage marker expression in M0 macrophages co-cultured with tumor cells.
Furthermore, interference with SLC3A2 increased levels of ROS, lipid peroxidation, and Fe2+ downregulated the expression of solute carrier family 7 member11 (SLC7A11) and glutathione peroxidase 4 (GPX4), while upregulated the expression of acyl-coA synthetase long-chain family member 4 (ACSL4) and transferrin receptor 1 (TFR1) in BLCA cells. However, the impact of SLC3A2 interference on cell proliferation and macrophage polarization was impeded by ferroptosis inhibitors.
The study concluded that interference with SLC3A2 effectively inhibited BLCA cell growth and the polarization of tumor-associated macrophages. This inhibition was achieved by promoting ferroptosis in BLCA cells.
No funding information was provided.
Source: https://pubmed.ncbi.nlm.nih.gov/38656249/
Wu P, Zhao L, Kong G, et al. (2024). “Study on the Role and Mechanism of SLC3A2 in Tumor-Associated Macrophage Polarization and Bladder Cancer Cells Growth.” Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241246649. doi: 10.1177/15330338241246649. PMID: 38656249; PMCID: PMC11044785.
