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

被引:21
作者
Kamoshida, Go [1 ]
Matsuda, Ayaka [1 ]
Miura, Risa [1 ]
Takashima, Yuri [1 ]
Katsura, Arisa [1 ]
Tsuji, Tsutomu [1 ]
机构
[1] Hoshi Univ, Dept Microbiol, Sch Pharm & Pharmaceut Sci, Shinagawa Ku, Tokyo 1428501, Japan
关键词
Monocytes; Tumor cell invasion; MMP-9; Fibronectin; TNF-alpha; TNF-ALPHA; EXTRACELLULAR-MATRIX; CANCER DEVELOPMENT; CARCINOMA-CELLS; MELANOMA-CELLS; KAPPA-B; MACROPHAGES; GROWTH; METASTASIS; INVASIVENESS;
D O I
10.1007/s10585-012-9536-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 alpha 5 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)-alpha from the conditioned medium with an antibody-protein G-Sepharose conjugate. In addition, the treatment of MKN1 cells with TNF-alpha promoted invasion of these cells, as well as secretion of MMP-9 and fibronectin. These results suggest that TNF-alpha secreted from monocytes is, at least in part, involved in the changes in invasive phenotype of tumor cells during co-culture with monocytes.
引用
收藏
页码:289 / 297
页数:9
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