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Research ArticleExperimental Studies

Soluble Factors Involved in Cancer Cell–Macrophage Interaction Promote Breast Cancer Growth

KIMIHIRO YONEMITSU, YUKO MIYASATO, TAKUYA SHIOTA, YUSUKE SHINCHI, YUKIO FUJIWARA, SEIJI HOSAKA, YUTAKA YAMAMOTO and YOSHIHIRO KOMOHARA
Anticancer Research September 2021, 41 (9) 4249-4258; DOI: https://doi.org/10.21873/anticanres.15229
KIMIHIRO YONEMITSU
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
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YUKO MIYASATO
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
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TAKUYA SHIOTA
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
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YUSUKE SHINCHI
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
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YUKIO FUJIWARA
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
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SEIJI HOSAKA
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
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YUTAKA YAMAMOTO
2Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Kumamoto, Japan;
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YOSHIHIRO KOMOHARA
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
3Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, Japan
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  • For correspondence: ycomo@kumamoto-u.ac.jp
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Abstract

Background/Aim: Recent studies have indicated the clinical significance of tumor-associated macrophages (TAMs) in breast cancer; however, the detailed mechanisms of cell–cell interactions between TAMs and cancer cells remain unclear. Materials and Methods: In vitro cell culture studies using human monocyte-derived macrophages and breast cancer cell lines were performed to test which cytokines would be involved in cell-cell interactions between cancer cells and macrophages. In addition, studies using human resected samples and animal breast cancer models were performed to examine the significance of TAMs in cancer development. Results: Osteopontin, HB-EGF, and IL-6 were suggested to be macrophage-derived growth factors for breast cancer cells. FROUNT inhibitor significantly blocked TAM infiltration and subcutaneous tumor growth in an E0771 mouse breast cancer model. Conclusion: TAMs express growth factors, such as osteopontin, for cancer cells, and targeting of TAM infiltration might be a promising approach for anti-breast cancer therapy.

Key Words:
  • Breast cancer
  • macrophage
  • osteopontin
  • HB-EGF
  • IL-6
  • FROUNT
  • Received June 30, 2021.
  • Revision received July 23, 2021.
  • Accepted July 26, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (9)
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September 2021
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Soluble Factors Involved in Cancer Cell–Macrophage Interaction Promote Breast Cancer Growth
KIMIHIRO YONEMITSU, YUKO MIYASATO, TAKUYA SHIOTA, YUSUKE SHINCHI, YUKIO FUJIWARA, SEIJI HOSAKA, YUTAKA YAMAMOTO, YOSHIHIRO KOMOHARA
Anticancer Research Sep 2021, 41 (9) 4249-4258; DOI: 10.21873/anticanres.15229

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Soluble Factors Involved in Cancer Cell–Macrophage Interaction Promote Breast Cancer Growth
KIMIHIRO YONEMITSU, YUKO MIYASATO, TAKUYA SHIOTA, YUSUKE SHINCHI, YUKIO FUJIWARA, SEIJI HOSAKA, YUTAKA YAMAMOTO, YOSHIHIRO KOMOHARA
Anticancer Research Sep 2021, 41 (9) 4249-4258; DOI: 10.21873/anticanres.15229
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Keywords

  • Breast cancer
  • macrophage
  • osteopontin
  • HB-EGF
  • IL-6
  • FROUNT
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