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Effect of macrophages on biological function of ovarian cancer cells in tumor microenvironment in vitro

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

To investigate the influence of two types of tumor-associated macrophages (TAMs) on the biological function of human ovarian cell lines in vitro.

Methods

(1) M2 macrophage release was induced by IL-4, and M1 macrophage release by phorbol myristate acetate (PMA) in vitro. Flow cytometry was used to distinguish these two types; (2) transwell culture system was used to establish a non-contact co-culture model of macrophage and ovarian cancer cells (SKOV3, HEY, HO8910 and A2780) in vitro. The microenvironment of ovarian cancer was simulated in vitro. (3) The proliferation, apoptosis, migration and invasion of ovarian cancer cells SKOV3, HEY, HO8910 and A2780 were analyzed after co-culture. Their proliferation was detected by CCK8 method, apoptosis by flow cytometry, Annexin V-FITC/PI double staining, invasion by Transwell assay, and migration by wound healing test.

Results

(1) IL-4-induced macrophages (M2) overexpressed CD163, and PMA-induced macrophages (M1) overexpressed HLA-DR. After co-culturing primary macrophages with ovarian cancer cells (SKOV3, HEY, HO8910, A2780), macrophage CD163 was highly expressed. (2) Proliferation and apoptosis of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the proliferation of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the apoptosis of ovarian cancer cells in M2 co-culture group decreased compared to that in M1 co-culture group and primary co-culture group (p < 0.05). (3) Migration and invasion of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the invasion of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the migration of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and the primary co-culture group (p < 0.05).

Conclusion

In the simulated in vitro tumor microenvironment, co-cultured ovarian cancer cells polarized macrophages to the M2 phenotype. Furthermore, M2 macrophages enhanced the proliferation, invasion and migration, and inhibited the apoptosis of ovarian cancer cells.

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Acknowledgements

Yi Jiang was supported by the National Natural Science Foundation of China (No. 81702566) and Wenjun Cheng was supported by the National Natural Science Foundation of China (No. 81872119).

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Author notes

  1. Jiang Yi and Yuan Lin contributed equally to this work.

Authors and Affiliations

  1. Gynecology Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Jiang Yi, Yuan Lin, Wan Yicong, Luo Chengyan, Zhou Shulin & Cheng Wenjun

Authors
  1. Jiang Yi
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  2. Yuan Lin
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  3. Wan Yicong
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  4. Luo Chengyan
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  5. Zhou Shulin
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  6. Cheng Wenjun
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Contributions

Yi Jiang is responsible for subject experiment and article writing. Lin Yuan is responsible for part of the subject experiment, such as cell proliferation and apoptosis. Yicong Wan is responsible for part of the article writing. Chengyan Luo is responsible for cell co-culture. Shulin Zhou is responsible for part of the subject experiment, such as transwell assay. Wenjun Cheng is responsible for Subject guidance.

Corresponding author

Correspondence to Cheng Wenjun.

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Yi, J., Lin, Y., Yicong, W. et al. Effect of macrophages on biological function of ovarian cancer cells in tumor microenvironment in vitro. Arch Gynecol Obstet 302, 1009–1017 (2020). https://doi.org/10.1007/s00404-020-05719-8

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  • DOI: https://doi.org/10.1007/s00404-020-05719-8

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