title: Effects of hyaluronic acid and CD44 interaction on the proliferation and invasiveness of malignant pleural mesothelioma.
abstract: Hyaluronic acid (HA) has been proposed as a biochemical marker of malignant pleural mesothelioma (MPM). The present study focused on the implications of HA and CD44 interaction in the proliferation and invasiveness of MPM. The proliferation and invasive activity was evaluated in two human mesothelioma cell lines, ACC-MESO-1 and K921MSO, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the transwell chamber model. The knockdown of CD44 gene expression was accomplished by transfection of the cells with small interfering RNA. Flow cytometry revealed that both the ACC-MESO-1 and K921MSO cell lines highly expressed CD44. Treatment with HA enhanced the proliferation in both mesothelioma cell lines in comparison to cells without HA treatment. The treatment with HA (25 μg/ml) also significantly upregulated the invasion of both types of cells. The silencing of CD44 significantly abrogated the effect of HA treatment on the proliferation of ACC-MESO-1 cells and significantly suppressed the proliferation of K921MSO cells. HA-CD44 binding is important for the migration and proliferation of mesothelioma cells. Therefore, the HA-CD44 interaction is a potentially useful therapeutic target in MPM.
authors.affiliation: Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Yahatanishi, Kitakyushu 807, Japan. hanagiri@med.uoeh-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hanagiri
authors.forename: Shinji
authors.initials: S
authors.lastname: Shinohara
authors.forename: Masaru
authors.initials: M
authors.lastname: Takenaka
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shigematsu
authors.forename: Manabu
authors.initials: M
authors.lastname: Yasuda
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Nagata
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: So
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D016066:Pleural Effusion, Malignant / Q000378:metabolism / Q000473:pathology*; D010997:Pleural Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid