Cancer-Associated Fibroblast-Derived Interleukin-8 Promotes Ovarian Cancer Cell Stemness and Malignancy Through the Notch3-Mediated Signaling

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 Jul 19

PMID 34277625

Citations 29

Authors

Zhaodong Ji

Wenjuan Tian

Wen Gao

Rongyu Zang

Huaying Wang

Gong Yang

Affiliations

Soon will be listed here.

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 IC 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.

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