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Cited by 75Immune cells in cancerCancer Cells and MetastasisMesenchymal stem cell research

Co-culture of Ovarian Cancer Stem-like Cells with Macrophages Induced SKOV3 Cells Stemness via IL-8/STAT3 Signaling

Ning, Yingxia, Cui, Yinghong, Li, Xiang, Cao, Xiaocheng, Chen, A., Xu, Chang, Cao, Jianguo, Luo, Xin·2018·Biomedicine & Pharmacotherapy
DOI 10.1016/j.biopha.2018.04.022
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Abstract

Among recent concepts in the cancer biology field, the tumor microenvironment is highly associated with cancer stem cells, and plays a key role in tumor progression. This study aimed to explore the mechanism that the stemness induction of SKOV3 cell line by macrophages derived from THP-1 cells, which was co-cultured with SKOV3-derived ovarian cancer stem-like cells (OCSLCs). Sphere formation, soft agar colony formation, and expression levels of CD133 and CD44 were assessed to reflect OCSLC properties. ELISA was used to evaluate secretion profile changes in macrophages co-cultured with or without SKOV3-derived OCSLCs. For mechanistic evaluation, rhIL-8, IL-8 neutralizing antibody (IL-8 Ab), signal transducer and activator of transcription 3 (STAT3) shRNA and STAT3 cDNA were used. The results showed that IL-10, VEGF, MMP-9, IL-8 secretion and CD163 and STAT3 expression levels in macrophages co-cultured with OCSLCs were increased compared with those from THP-1 cells, while IL-12 and NO amounts were significantly reduced, reflecting M2 macrophage polarization. Addition of rhIL-8 to THP-1 cell conditioned media promoted M2 macrophage polarization and stemness in SKOV3 cells, which were suppressed by IL-8 Ab addition to co-culture conditioned media. Consistently, overexpression of STAT3 induced M2 macrophage polarization and stemness in SKOV3 cells, which were inhibited by STAT3 knockdown in macrophages from THP-1 cells. Importantly, STAT3 overexpression rescued the effects of IL-8 Ab on M2 macrophage polarization and stemness in SKOV3 cells. These results suggested that stemness induction in SKOV3 cells by macrophages co-cultured with SKOV3-derived OCSLCs involved IL-8/STAT3 signaling.

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Crossref · 10.1016/j.biopha.2018.04.022

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  • Co-cultures of ovarian cancer cells and macrophages have identified positive feedback loops that drive stemness, chemoresistance and spheroid formation in cancer cells and M2 polarization of macrophages.

    “Co-cultures of ovarian cancer cells and macrophages have identified positive feedback loops that drive stemness, chemoresistance and spheroid formation in cancer cells and M2 polarization of macrophages (Long et al., 2018; Ning et al., 2018; Raghavan et al., 2019).”

    From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Ning et al., 2018

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Authors
Ning, Y., Cui, Y., Li, X., Cao, X., Chen, A., Xu, C., Cao, J., & Luo, X.
Affiliations
  • First Affiliated Hospital of Guangzhou Medical University (CN)
  • Hunan Normal University (CN)
  • First Affiliated Hospital of Jinan University (CN)
Corresponding author
  • Cao, Jianguo
  • Luo, Xin
ORCID
Venue
Biomedicine & Pharmacotherapy
Publisher
Elsevier BV
Published
2018-07
Volume
103
Pages
262-271
ISSN
0753-3322 (ISSN-L)
DOI
10.1016/j.biopha.2018.04.022
OpenAlex
W2800030611
Cited by
75
References
36
Citations by year
2026: 4 · 2025: 9 · 2024: 7 · 2023: 13 · 2022: 15 · 2021: 9 · 2020: 11 · 2019: 6 · 2018: 1
FWCI
2.91
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Biomedicine & Pharmacotherapy (publishedVersion)
  • PubMed (publishedVersion)
Funders
Guangzhou Medical University ([2017]210)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
macrophages, tumor microenvironment, M2 macrophage polarization, cancer stemness, SKOV3 cells, THP-1 cells, co-culture, CD133, CD44, IL-10, vascular endothelial growth factor, MMP-9, CD163
MeSH terms
Animals, Female, Humans, Macrophages, Mice, Inbred BALB C, Ovarian Neoplasms, Phenotype, Recombinant Proteins, Neoplastic Stem Cells, Signal Transduction, Interleukin-8, Cell Polarity, Culture Media, Conditioned, Coculture Techniques, Cell Line, Tumor, STAT3 Transcription Factor, Gene Knockdown Techniques, Antibodies, Neutralizing

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