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Báo cáo khoa học: Acidic extracellular pH increases calcium influx-triggered phospholipase D activity along with acidic sphingomyelinase activation to induce matrix metalloproteinase-9 expression in mouse metastatic melanoma
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Acidic extracellular pH is a common feature of tumor tissues. We have reported that culturing cells at acidic pH (5.4–6.5) induced matrix metallo-proteinase-9 expression through phospholipase D, extracellular signal regu-lated kinase 1⁄2 and p38 mitogen-activated protein kinases and nuclear factor-jB. | ỊFEBS Journal Acidic extracellular pH increases calcium influx-triggered phospholipase D activity along with acidic sphingomyelinase activation to induce matrix metalloproteinase-9 expression in mouse metastatic melanoma Yasumasa Kato1 2 Shigeyuki Ozawa1 3 Mamoru Tsukuda2 Eiro Kubota3 Kaoru Miyazaki4 Yves St-Pierre5 and Ryu-Ichiro Hata1 1 Department of Biochemistry and Molecular Biology Kanagawa DentalCollege Yokosuka Japan 2 Department of Biology and Function in the Head and Neck Yokohama City University Graduate Schoolof Medicine Japan 3 Department of Oraland MaxillofacialSurgery Kanagawa DentalCollege Yokosuka Japan 4 Division of Cell Biology Kihara Institute for BiologicalResearch Yokohama City University Japan 5 INRS-Institut Armand-Frappier Universite du Quebec Laval Quebec Canada Keywords acidic sphingomylinase Ca2 influx extracellular acidic pH MMP-9 Correspondence Y. Kato Department of Biochemistry and Molecular Biology Kanagawa Dental College Yokosuka 238-8580 Japan Fax 81 46 822 8839 Tel 81 46 822 8840 E-mail yasumasa@kdcnet.ac.jp Received 23 January 2007 revised 23 April 2007 accepted 27 April 2007 doi 10.1111 j.1742-4658.2007.05848.x Acidic extracellular pH is a common feature of tumor tissues. We have reported that culturing cells at acidic pH 5.4 6.5 induced matrix metalloproteinase-9 expression through phospholipase D extracellular signal regulated kinase 1 2 and p38 mitogen-activated protein kinases and nuclear factor-KB. Here we show that acidic extracellular pH signaling involves both pathways of phospholipase D triggered by Ca2 influx and acidic sphingomyelinase in mouse B16 melanoma cells. We found that BAPTA-AM 1 2-bis 2-aminophenoxy -ethane-N N N N -tetraacetic acid tetrakis acetoxymethyl ester a chelator of intracellular free calcium and the voltage dependent Ca2 channel blockers mibefradil for T-type and nimodipine for L-type dose-dependently inhibited acidic extracellular pH-induced matrix metalloproteinase-9 expression. Intracellular free