Abstract 2992: miR-200-mediated inactivation of cancer-associated fibroblasts attenuates lung cancer invasion and metastasis

Abstract Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment and contribute to the development and progression of lung cancer. We aimed to elucidate whether miRNA-200 (miR-200), which is recognized for its ability to suppress EMT, prevents CAFs from promoting cancer progression. Inactivation of CAFs mediated by miR-200 suppressed lung cancer cell invasion, migration, tumorigenesis, and metastasis. Additionally, miR-200 attenuated the ability of CAFs to facilitate the aggressiveness of lung cancer cells, encourage M2 polarization of macrophages, and increase the angiogenic sprouting of vascular endothelial cells. NRP2, known as a co-receptor of VEGFR, was identified as a target of miR-200, mediating the functional activity of miR-200 in CAFs. NRP2-VEGFR signaling promoted the secretion of VEGFD and PTN from CAFs to activate cancer cell migration and invasion. Based on these findings, we suggest that miR-200 impedes cancer progression and metastasis by remodeling CAFs, and that miR-200 and NRP2 are potential therapeutic targets in the treatment of lung cancer. Citation Format: Inyoung Cheon, Sieun Lee, Young-Ho Ahn. miR-200-mediated inactivation of cancer-associated fibroblasts attenuates lung cancer invasion and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2992.