title: ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells.
abstract: Cancer cells contain a small population of cancer stem cells or cancer initiating cells, which can be enriched in the side population (SP) after fluorescence activated cell sorting. To examine the members of the ADAM, ADAMTS and MMP gene families related to phenotypes of the SP and the main population (MP), we screened the expression of all the members in the propagated SP and MP of A549 lung adenocarcinoma cells, and found that the relative expression ratio of ADAM23 in the MP to the SP is most highly increased, but none of them are increased in the SP. A similar result on the ADAM23 expression was obtained with another cell line, Calu-3 cells. Overexpression of ADAM23 inhibited colony formation, cell adhesion and migration, and knockdown of ADAM23 by shRNA showed the reverse effects. ADAM23-mediated suppression of colony formation, cell adhesion and migration was greatly reduced by treatment with neutralizing anti-ADAM23 antibody, anti-αvβ3 integrin antibody and/or ADAM23 disintegrin peptide. Expression of cancer stem cell-related genes, including AKRC1/2, TM4SF1 and NR0B1, was increased by knockdown of ADAM23. In addition, lung metastasis of A549 transfectants with different levels of ADAM23 expression was negatively regulated by the ADAM23 expression levels. Our data provide evidence that ADAM23 plays a role in suppression of cancer cell progression through interaction with αvβ3 integrin, and suggest that downregulation of ADAM23 in SP cells may contribute toward providing a cancer stem cell phenotype by facilitating the activity of integrin αvβ3.
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.|Second Department of Internal Medicine and Respiratory Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Mochizuki
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Miyamae
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Second Department of Internal Medicine and Respiratory Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.|Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis* / Q000235:genetics; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D058985:Side-Population Cells / Q000473:pathology
chemical_list: D039302:Integrin alphaVbeta3; D051722:ADAM Proteins; C114633:ADAM23 protein, human
keywords: ADAM23; colony formation; metastasis; non-small cell lung carcinoma cells; side population