title: Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer.
abstract: Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with nonsmall cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that downregulation of several members of tetraspanins is associated with progression of solid tumors, thus indicating poor prognosis. Here we screened 30 lung cancer cell lines for expression of tetraspanins, CD9, CD63, CD81, CD82, CD151, and NAG-2. Flow cytometry revealed that, among these proteins, CD9 is broadly expressed in NSCLC lines, but is absent or highly reduced in most SCLC lines (P<0.0001). Using the Boyden chamber and videomicroscopic cell motility assays, we showed that stable transfection of CD9 into an SCLC line, OS3-R5, reduced cell motility on fibronectin. Furthermore, by transient transfection of green fluorescent protein (GFP)-tagged CD9 into three other SCLC lines, we observed that SCLC cells expressing GFP-CD9 were uniformly less motile than untransfected cells. CD9 or GFP-CD9 was associated with beta1 integrins and distributed at the tumor cell periphery and cell-cell contacts, suggesting that CD9 modifies beta1 integrin function to reduce motility. These findings suggest that low expression of CD9 may contribute to the highly invasive and metastatic phenotype of SCLC.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Funakoshi
authors.forename: Isao
authors.initials: I
authors.lastname: Tachibana
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kimura
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kijima
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nishino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Goto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoneda
authors.forename: Toru
authors.initials: T
authors.lastname: Kumagai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Osaki
authors.forename: Seiji
authors.initials: S
authors.lastname: Hayashi
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000503:physiopathology; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000503:physiopathology; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D015536:Down-Regulation; D017930:Genes, Reporter; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D060245:Tetraspanin 29; D014162:Transfection
chemical_list: D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29