Modulation of matrix metalloproteinase-9 secretion from tumor-associated macrophage-like cells by proteolytically processed laminin-332 (laminin-5)

• Published in: Clinical & experimental metastasis 2014-03, Vol.31 (3), p.285-291
• Main Authors: Kamoshida, Go, Ogawa, Takashi, Oyanagi, Jun, Sato, Hiroki, Komiya, Eriko, Higashi, Shouichi, Miyazaki, Kaoru, Tsuji, Tsutomu
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Adhesion; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Differentiation - genetics; Cell Line, Tumor; Coculture Techniques; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Hematology; Humans; Kalinin; Macrophages - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Monocytes - cytology; Neoplasms - genetics; Neoplasms - pathology; Oncology; Research Paper; Surgical Oncology
• ISSN: 0262-0898; 1573-7276
• DOI: 10.1007/s10585-013-9627-0

Macrophages infiltrating tumor tissues (tumor-associated macrophages, TAM) affect the malignant behaviors of tumor cells. We previously reported that monocytes were differentiated into TAM-like cells secreting matrix metalloproteinase (MMP)-9 by co-culture with tumor cells, and that cell adhesion to extracellular matrix (ECM) proteins played a critical role in the differentiation. In this study, we found that the monocyte differentiation was promoted by laminin-332 (laminin-5), a major epithelial ECM component. We also demonstrated that the proteolytic processing of the γ2 chain of laminin-332 was essential for its activity but that the N-terminal short arm of the γ2 chain inhibited MMP-9 secretion. These results indicate that the activity of laminin-332 for monocyte differentiation is dynamically regulated by the proteolytic processing of the γ2 chain.