title: Monocyte differentiation induced by co-culture with tumor cells involves RGD-dependent cell adhesion to extracellular matrix.
abstract: Macrophages that infiltrate tumor tissues, or tumor-associated macrophages (TAMs), affect the malignant behaviors of tumor cells. In this study, we attempted to induce monocytes to differentiate into TAM-like cells producing matrix metalloproteinases (MMPs) by co-culture with tumor cells. When human monocytes were co-cultured for 3-7 days with tumor cell lines, monocytes differentiated to produce MMP-9, accompanied by morphological changes. The in vitro cell invasion of MKN1 human gastric carcinoma cells into Matrigel membranes was promoted in the presence of differentiated monocytes, and the enhancement of cell invasion by differentiated monocytes was correlated with their MMP-9 productivity. The addition of an RGD (Arg-Gly-Asp) peptide to the culture significantly inhibited monocyte differentiation. The MMP-9 production from monocytes was diminished by the depletion of fibronectin from the conditioned media with gelatin-Sepharose, and potentiated by culturing them in fibronectin-coated plates. These results suggest that cell adhesion to the extracellular matrix plays a crucial role in monocyte differentiation into TAM-like cells.
authors: Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Go
authors: G
authors: Kamoshida
authors: Ayaka
authors: A
authors: Matsuda
authors: Wakana
authors: W
authors: Sekine
authors: Hiromi
authors: H
authors: Mizuno
authors: Teruaki
authors: T
authors: Oku
authors: Saotomo
authors: S
authors: Itoh
authors: Tatsuro
authors: T
authors: Irimura
authors: Tsutomu
authors: T
authors: Tsuji
mesh_terms: D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008264:Macrophages / Q000166:cytology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D009842:Oligopeptides / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology
chemical_list: D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D020780:Matrix Metalloproteinase 9