title: Non-thermal atmospheric pressure plasma inhibits thyroid papillary cancer cell invasion via cytoskeletal modulation, altered MMP-2/-9/uPA activity.
abstract: Plasma, the fourth state of matter, is defined as a partially or completely ionized gas that includes a mixture of electrons and ions. Advances in plasma physics have made it possible to use non-thermal atmospheric pressure plasma (NTP) in cancer research. However, previous studies have focused mainly on apoptotic cancer cell death mediated by NTP as a potential cancer therapy. In this study, we investigated the effect of NTP on invasion or metastasis, as well as the mechanism by which plasma induces anti-migration and anti-invasion properties in human thyroid papillary cancer cell lines (BHP10-3 and TPC1). Wound healing, pull-down, and Transwell assays demonstrated that NTP reduced cell migration and invasion. In addition, NTP induced morphological changes and cytoskeletal rearrangements, as detected by scanning electron microscopy and immunocytochemistry. We also examined matrix metalloproteinase (MMP)-2/-9 and urokinase-type plasminogen activator (uPA) activity using gelatin zymography, uPA assays and RT-PCR. FAK, Src, and paxillin expression was detected using Western blot analyses and immunocytochemistry. NTP decreased FAK, Src, and paxillin expression as well as MMP/uPA activity. In conclusion, NTP inhibited the invasion and metastasis of BHP10-3 and TPC1 cells by decreasing MMP-2/-9 and uPA activities and rearranging the cytoskeleton, which is regulated by the FAK/Src complex. These findings suggest novel actions for NTP and may aid in the development of new therapeutic strategies for locally invasive and metastatic cancers.
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
authors.forename: Kang Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Seo
authors.affiliation: Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
authors.forename: Sang Sik
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Department of Molecular Science and Technology and Department of Life Science, Ajou University, Suwon, Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology and Department of Life Science, Ajou University, Suwon, Korea.
authors.forename: Eunpyo
authors.initials: E
authors.lastname: Moon
authors.affiliation: Plasma Systems and Materials (PSM) America Inc., Colorado Springs, Colorado, United States of America.
authors.forename: Keunho
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002291:Carcinoma, Papillary; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D058626:Plasma Gases / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D058626:Plasma Gases; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9