title: A novel functional site of extracellular matrix metalloproteinase inducer             (EMMPRIN) that limits the migration of human uterine cervical carcinoma cells.
abstract: EMMPRIN (extracellular matrix metalloproteinase inducer)/CD147, a membrane-bound             glycoprotein with two extracellular loop domains (termed loops I and II), progresses             tumor invasion and metastasis by increasing the production of matrix metalloproteinase             (MMP) in peritumoral stoma cells. EMMPRIN has also been associated with the control             of migration activity in some tumor cells, but little is known about how EMMPRIN             regulates tumor cell migration. In the present study, EMMPRIN siRNA suppressed             the gene expression and production of EMMPRIN in human uterine cervical carcinoma             SKG-II cells. An in vitro scratch wound assay showed enhancement of migration             of EMMPRIN-knockdown SKG-II cells. In addition, the SKG-II cell migration was             augmented by adding an E. coli-expressed human EMMPRIN mutant with two extracellular             loop domains (eEMP-I/II), which bound to the cell surface of SKG-II cells. However,             eEMP-I/II suppressed the native EMMPRIN-mediated augmentation of proMMP-1/procollagenase-1             production in a co-culture of the SKG-II cells and human uterine cervical fibroblasts,             indicating that the augmentation of SKG-II cell migration resulted from the interference             of native EMMPRIN functions by eEMP-I/II on the cell surface. Furthermore, a systematic             peptide screening method using nine synthetic EMMPRIN peptides coding the loop             I and II domains (termed EM1-9) revealed that EM9 (170HIENLNMEADPGQYR184) facilitated             SKG-II cell migration. Moreover, SKG-II cell migration was enhanced by administration             of an antibody against EM9, but not EM1 which is a crucial site for the MMP inducible             activity of EMMPRIN. Therefore, these results provide novel evidence that EMMPRIN             on the cell surface limits the cell migration of human uterine cervical carcinoma             cells through 170HIENLNMEADPGQYR184 in the loop II domain. Finally, these results             should provide an increased understanding of the functions of EMMPRIN in malignant             cervical carcinoma cells, and could contribute to the development of clinical             strategies for cervical cancer therapy.
authors: Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. satotak@toyaku.ac.jp
authors: Takashi
authors: T
authors: Sato
authors: Mami
authors: M
authors: Watanabe
authors: Kei
authors: K
authors: Hashimoto
authors: Tomoko
authors: T
authors: Ota
authors: Noriko
authors: N
authors: Akimoto
authors: Keisuke
authors: K
authors: Imada
authors: Motoyoshi
authors: M
authors: Nomizu
authors: Akira
authors: A
authors: Ito
mesh_terms: D000595:Amino Acid Sequence; D051926:Basigin / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C497886:BSG protein, human; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D051926:Basigin