Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston, Houston, TX, 77030, USA.
Nat Commun. 2020 Jul 15;11(1):3546. doi: 10.1038/s41467-020-17383-2.
Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.
高级卵巢癌通常会扩散到网膜。然而，调节其进展的间皮细胞衍生的分子决定因素尚未得到充分描述。在这里，我们表明，循环 ITLN1 在晚期卵巢癌患者中有预后意义。进一步的研究表明，ITLN1 通过降低 MMP1 的表达和诱导转移性卵巢癌细胞的代谢转变来抑制乳铁蛋白对卵巢癌细胞侵袭潜力和增殖的作用。此外，用 ITLN1 治疗的卵巢癌荷瘤小鼠表现出肿瘤生长速度的显著下降。这些数据表明，间皮细胞衍生的 ITLN1 在网膜肿瘤微环境中的下调促进了卵巢癌的进展。
