Potentiation of tumor cell invasion by co-culture with monocytes accompanying enhanced production of matrix metalloproteinase and fibronectin.
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.
Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
Go
G
Kamoshida
Ayaka
A
Matsuda
Risa
R
Miura
Yuri
Y
Takashima
Arisa
A
Katsura
Tsutomu
T
Tsuji
D015153:Blotting, Western; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005353:Fibronectins / Q000096:biosynthesis*; D005434:Flow Cytometry; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D009000:Monocytes / Q000473:pathology*; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017077:Culture Media, Conditioned; D005353:Fibronectins; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases