title: Transforming growth factor alpha promotes osteosarcoma metastasis by ICAM-1 and PI3K/Akt signaling pathway.
abstract: Osteosarcoma is the most common primary malignancy of bone and is characterized by a high malignant and metastatic potential. Transforming growth factor alpha (TGF-α) is classified as the EGF (epidermal growth factor)-like family, which is involved in cancer cellular activities such as proliferation, motility, migration, adhesion and invasion abilities. However, the effect of TGF-α on human osteosarcoma is largely unknown. We found that TGF-α increased the cell migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced TGF-α-mediated cell migration. We also found that the phosphatidylinositol 3'-kinase (PI3K)/Akt/NF-κB pathway was activated after TGF-α treatment, and TGF-α-induced expression of ICAM-1 and cell migration was inhibited by the specific inhibitors and siRNAs of PI3K, Akt, and NF-κB cascades. In addition, knockdown of TGF-α expression markedly decreased cell metastasis in vitro and in vivo. Our results indicate that TGF-α/EGFR interaction elicits PI3K and Akt activation, which in turn activates NF-κB, resulting in the expression of ICAM-1 and contributing the migration of human osteosarcoma cells.
authors.affiliation: Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-Han
authors.initials: CH
authors.lastname: Hou
authors.affiliation: Department of Dermatology, Sijhih Cathay General Hospital, Taipei, Taiwan.
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Lin
authors.affiliation: Veterinarian Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Kai-Biao
authors.initials: KB
authors.lastname: Tong
authors.affiliation: Department of Orthopedic Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. Electronic address: shengmou@ms.skh.org.tw.
authors.forename: Sheng-Mon
authors.initials: SM
authors.lastname: Hou
authors.affiliation: Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. Electronic address: anti0822@hotmail.com.
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D066246:ErbB Receptors / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D058539:Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C573420:ICAM1 protein, human; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; C587886:TGFA protein, human; D016211:Transforming Growth Factor alpha; D018799:Intercellular Adhesion Molecule-1; D058539:Phosphatidylinositol 3-Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Migration; Osteosarcoma; TGF-α