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Potentiation of tumor cell invasion by co-culture with monocytes accompanying enhanced production of matrix metalloproteinase and fibronectin

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Abstract

Macrophages are a major population of immune cells, and those that infiltrate into tumor tissues and affect the malignant behavior of tumor cells are called tumor-associated macrophages (TAMs). We previously reported that human peripheral blood monocytes could be induced in vitro to differentiate into TAM-like cells by co-culture with tumor cells. In the present study, we characterized changes in the invasive phenotype of tumor cells after co-culture with monocytes, and found that MKN1 gastric carcinoma cells acquired higher invasive potential into Matrigel-reconstituted basement membranes, accompanied by enhanced production of matrix metalloproteinase (MMP)-9. The increased invasiveness was inhibited in the presence of an arginyl–glycyl–aspartic acid peptide, suggesting that the process is dependent on the integrin-extracellular matrix interaction. We also found that these cells secreted fibronectin into the culture medium and expressed α5 integrin on their surface at higher levels after the co-culture with monocytes for 5 days. The conditioned medium of monocytes also potentiated MKN1 cell invasion; however, the potentiation was lowered by the depletion of tumor necrosis factor (TNF)-α from the conditioned medium with an antibody-protein G-Sepharose conjugate. In addition, the treatment of MKN1 cells with TNF-α promoted invasion of these cells, as well as secretion of MMP-9 and fibronectin. These results suggest that TNF-α secreted from monocytes is, at least in part, involved in the changes in invasive phenotype of tumor cells during co-culture with monocytes.

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Abbreviations

ECM:

Extracellular matrix

FCS:

Fetal calf serum

MMP:

Matrix metalloproteinase

RGD:

Arginyl–glycyl–aspartic acid

TNF-α:

Tumor necrosis factor-α

TAM:

Tumor-associated macrophage

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Acknowledgments

We are grateful to Dr. Masaaki Kurihara (Kurihara Clinic, Tokyo, Japan), Dr. Saotomo Itoh (Nagoya City University), Dr. Makoto Tsuiji and Dr. Teruaki Oku (Hoshi University School of Pharmacy and Pharmaceutical Sciences) for their helpful discussions. We would also like to thank Ms. Sayuri Suzuki, Mr. Takaki Miyajima, Mr. Michirou Ishiwa, and Mr. Yugo Nishimura (Hoshi University School of Pharmacy and Pharmaceutical Sciences) for their technical assistance. This study was supported in part by the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Open Research Center Project.

Conflicts of interest

The authors have no potential conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Go Kamoshida, Ayaka Matsuda, Risa Miura, Yuri Takashima, Arisa Katsura & Tsutomu Tsuji

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  1. Go Kamoshida
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  2. Ayaka Matsuda
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Correspondence to Tsutomu Tsuji.

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Kamoshida, G., Matsuda, A., Miura, R. et al. Potentiation of tumor cell invasion by co-culture with monocytes accompanying enhanced production of matrix metalloproteinase and fibronectin. Clin Exp Metastasis 30, 289–297 (2013). https://doi.org/10.1007/s10585-012-9536-7

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  • DOI: https://doi.org/10.1007/s10585-012-9536-7

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