%PDF-1.3 % 1 0 obj << /Type /Pages /Count 6 /Kids [ 3 0 R 4 0 R 5 0 R 6 0 R 7 0 R 8 0 R ] >> endobj 2 0 obj << /Producer (PyPDF2) /Title (Front\055cell\055specific\040expression\040of\040membrane\055type\0401\040matrix\040metalloproteinase\040and\040gelatinase\040A\040during\040cohort\040migration\040of\040colon\040carcinoma\040cells\040induced\040by\040hepatocyte\040growth\040factor\057scatter\040factor\056) /Author (Kazuki\040Nabeshima\054\040Teruhiko\040Inoue\054\040Yoshiya\040Shimao\054\040Yasunori\040Okada\054\040Yoshifumi\040Itoh\054\040Motoharu\040Seiki\054\040Masashi\040Koono) /Subject (Migration\040of\040tumor\040cells\040is\040usually\040assessed\040as\040single\040cell\040locomotion\040in\040vitro\040using\040Boyden\040chamber\040type\040assays\056\040In\040vivo\054\040however\054\040carcinoma\040cells\040frequently\040invade\040the\040surrounding\040tissue\040as\040coherent\040clusters\040or\040nests\040of\040cells\056\040We\040have\040called\040this\040type\040of\040movement\040\042cohort\040migration\042\040and\040developed\040a\040two\055dimensional\040in\040vitro\040cohort\040migration\040model\054\040in\040which\040human\040rectal\040well\055differentiated\040adenocarcinoma\040cells\040\050L\05510\051\040migrate\040from\040piled\055up\040cell\040islands\040as\040coherent\040sheets\040of\040cells\040when\040stimulated\040with\040hepatocyte\040growth\040factor\057scatter\040factor\056\040In\040this\040study\054\040we\040examined\040whether\040there\040is\040a\040cohort\040migration\055specific\040way\040of\040expression\040of\040matrix\040metalloproteinases\040\050MMP\051\040and\040whether\040degradation\040of\040extracellular\040matrix\040is\040necessary\040for\040this\040type\040of\040migration\056\040Production\040of\040membrane\055type\0401\055MMP\040\050MT1\055MMP\051\040and\040gelatinase\040A\040\050MMP\0552\051\040by\040L\05510\040cells\040was\040demonstrated\040by\040gelatin\040zymography\054\040immunoblotting\054\040and\040reverse\040transcription\055PCR\056\040When\040cohort\040migration\040was\040induced\040with\040hepatocyte\040growth\040factor\057scatter\040factor\054\040MT1\055MMP\040and\040MMP\0552\040were\040immunolocalized\040predominantly\040in\040the\040leading\040edges\040of\040the\040front\040cells\040of\040migrating\040cell\040sheets\054\040with\040the\040following\040cells\040being\040negative\056\040In\040addition\054\040during\040the\040cohort\040migration\040on\040gelatin\055coated\040substratum\054\040the\040gelatin\040matrix\040was\040degraded\040by\040the\040cells\054\040in\040a\040very\040organized\040manner\054\040causing\040radially\040arrayed\040lysis\040of\040gelatin\040matrix\040at\040the\040sites\040of\040leading\040edges\056\040BB94\054\040a\040synthetic\040inhibitor\040specific\040to\040MMPs\054\040tissue\040inhibitor\040of\040metalloproteinases\0551\040and\040\0552\054\040and\040the\040COOH\055terminal\040hemopexin\055like\040domain\040of\040MMP\0552\040inhibited\040the\040migration\040on\040gelatin\040matrix\056\040Thus\054\040these\040data\040demonstrate\040that\040gelatin\040matrix\040is\040reorganized\040to\040suit\040cell\040migration\040via\040leading\055edge\055of\055front\055cell\055specific\040localization\040of\040MT1\055MMP\040and\040MMP\0552\040during\040cohort\040migration\040and\040suggest\040that\040the\040reorganization\040is\040essential\040for\040this\040type\040of\040migration\056) 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