Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 113, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.109422
Keywords
Erastin; TAMs; Metastasis; STAT3; IL-8
Categories
Funding
- National Natural Science Foundation of China [81874101]
- Science and Technology Commission of Shanghai Municipality [18411963100]
- Project of Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161412]
- Shanghai Sailing Program [20YF1425200]
- Shanghai Municipal Commission of Health and Family Planning [2017ZZ02016]
Ask authors/readers for more resources
This study found that low concentration of erastin greatly promoted invasion and migration of ferroptosis-resistant OC cells through STAT3-mediated M2 polarization of macrophages. Additionally, erastin increased IL-8 production of macrophages, and blockade of IL-8 partially eliminated the stimulatory effect of erastin on ferroptosis-resistant OC cells.
Erastin is a small molecule identified in chemical screen that is capable of inducing ferropotosis. There is col-lective evidence proving that erastin-induced ferroptosis exhibits anti-tumor potential within diverse caners, such as ovarian cancer (OC). However, most OC cells show relative resistance to ferroptosis induced by erastin. M2-polarized tumor-associated macrophages (TAMs) have an important effect on the OC tumor microenviron-ment (TME), which makes M2 polarization a noticeable part in the context of OC therapy. The immunomodu-latory effects of erastin on ferroptosis-resistant OC cells remain poorly understood. Here, we found that low concentration of erastin greatly promoted ferroptosis-resistant OC cell invasion and migration via STAT3-mediated M2 polarization of macrophages. As revealed by in-vitro experimental results, erastin significantly increased metastases of ferroptosis-resistant OC, and the percentage of M2 macrophage infiltration was also raised after erastin treatment. Furthermore, erastin augmented IL-8 production of macrophages, and pharma-cological blockage of IL-8 partially abrogated the stimulatory effect of erastin on ferroptosis-resistant OC cells. This study demonstrates a new mechanism undering the tumor-promoting activity of erastin and has implications for the STAT3/IL-8 axis as a potential target for ferroptosis-resistant OC cells to improve overall anti-tumor efficacy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available