AUTHOR=Ji Zhaodong , Tian Wenjuan , Gao Wen , Zang Rongyu , Wang Huaying , Yang Gong TITLE=Cancer-Associated Fibroblast-Derived Interleukin-8 Promotes Ovarian Cancer Cell Stemness and Malignancy Through the Notch3-Mediated Signaling JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.684505 DOI=10.3389/fcell.2021.684505 ISSN=2296-634X ABSTRACT=

As a significant component in ovarian cancer microenvironment, cancer-associated fibroblasts (CAFs) contribute to cancer progression through interaction with cancer cells. Recent studies demonstrate that interleukin-8 (IL-8) is overexpressed in multiple cancer types and is essential for tumor development. Nonetheless, the underlying mechanism that the CAF-derived IL-8 promotes ovarian tumorigenesis is unknown. Here, we show that IL-8 secreted from CAFs could activate normal ovarian fibroblasts (NFs) through multiple signaling and that IL-8 stimulated malignant growth of ovarian cancer cells in animals and increased the IC50 of cisplatin (CDDP) in ovarian cancer cells. Further study showed that IL-8 induced cancer cell stemness via the activation of Notch3 and that the high level of IL-8 in ascites was positively correlated with the expression of Notch3 in ovarian cancer tissues. Collectively, IL-8 secreted from CAFs and cancer cells promotes stemness in human ovarian cancer via the activation of the Notch3-mediated signaling, which may provide a novel strategy for ovarian cancer treatment.