The secreted protein SPARCL1 suppresses tumor progression in papillary thyroid carcinoma via SLC3A2-mediated...

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid malignancy, where invasive growth and distant metastasis contribute to a worsened patient prognosis. SPARCL1, a known tumor suppressor gene in various cancers, encodes a secreted glycoprotein. Preliminary research suggests that elevated expression of SPARCL1 is correlated with a better prognosis in PTC, highlighting its potential as an innovative restorative therapeutic agent, but its specific role and underlying mechanisms remain unclear. This study aimed to investigate the impact of SPARCL1 on the invasion and metastasis of PTC cells by constructing an overexpression model of SPARCL1 in PTC cells through viral transduction, collecting the supernatant proteins from the PTC cell model and adding them to PTC cells, and introducing recombinant SPARCL1 protein into PTC cells. In addition, we conducted animal experiments to detect the effects of SPARCL1 on the subcutaneous tumor formation and multi-organ metastasis of PTC cells in mice, as well as the inhibitory effect of recombinant SPARCL1 on tumors formed by PTC cells. The findings revealed that overexpression of the SPARCL1 gene, the secretory form of the SPARCL1 protein, and the recombinant SPARCL1 protein all significantly inhibited the malignant biological behaviors of PTC cells. Overexpression of SPARCL1 can inhibit the subcutaneous growth of tumor cells and their metastasis to the lungs, liver, and kidneys of mice, and recombinant SPARCL1 protein can also inhibit the growth of subcutaneous tumors. Mechanistically, SPARCL1 appears to mediate its anti-tumor effects through the SLC3A2-mediated ferroptosis pathway, suggesting a novel mechanism by which SPARCL1 influences PTC progression. In summary, SPARCL1 inhibits the proliferation, invasion, and metastasis of PTC, highlighting its potential as a candidate for innovative restorative therapies in PTC treatment.