MUC5AC production is downregulated in NCI-H292 lung cancer cells cultured on type-IV collagen

• Published in: Molecular and cellular biochemistry 2010-04, Vol.337 (1-2), p.65-75
• Main Authors: Iwashita, Jun, Yamamoto, Tetsuya, Sasaki, Yoshiko, Abe, Tatsuya
• Format: Article
• Language: English
• Subjects: Asthma; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell Adhesion - drug effects; Cell Count; Cell Culture Techniques; Cell Proliferation - drug effects; Cellular biology; Collagen; Collagen - pharmacology; Collagen Type IV - pharmacology; Down-Regulation - drug effects; Down-Regulation - genetics; Drug Combinations; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Glycoproteins; Humans; Kinases; Laminin - pharmacology; Life Sciences; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical Biochemistry; Mucin 5AC - genetics; Mucin 5AC - metabolism; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - pathology; Oncology; Protein Kinase Inhibitors - pharmacology; Proteoglycans - pharmacology; src-Family Kinases - antagonists & inhibitors; Toy industry; Tumor Cells, Cultured
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-009-0286-z

Mucus overproduction is an important feature of bronchial asthma. MUC5AC mucin is a major component of mucus and is overproduced in patients with asthma. Although regulation of MUC5AC production has been well investigated, its regulation through the signals from extracellular matrix (ECM) is less clear. In this study, we investigated whether the signals from ECM regulate MUC5AC production in the human lung epithelial cell line NCI-H292. We found that MUC5AC production is downregulated in NCI-H292 cells cultured on type-IV collagen, a major component of ECM, but shows no obvious changes when cultured on type-I collagen or fibronectin. In contrast, MUC5AC production was upregulated on laminin and on reconstituted basement membrane (Matrigel), a complex of ECM components. Antibody-mediated inhibition of integrin β1-subunit, a major receptor involved in the adherence of cells to type-IV collagen, upregulated the MUC5AC production in NCI-H292 cells, and also in the cells cultured on type-IV collagen. Although the major signaling pathway from integrins is via Src kinase activation, treatment of cells with PP2, a Src kinase inhibitor, did not recover the downregulation of MUC5AC on type-IV collagen. In contrast, on Matrigel, the inhibition of integrin β1-subunit did not abolish the upregulation of MUC5AC production, but PP2 reduced the upregulation. These results suggest that ECM and an integrin/Src pathway play an important role in the regulation of MUC5AC production in the cell line NCI-H292. The production of MUC5AC is downregulated on type-IV collagen through a Src-independent pathway. In contrast, MUC5AC is upregulated on Matrigel through a Src-dependent pathway in NCI-H292 cells.