title: Ameloblastin induces tumor suppressive phenotype and enhances chemosensitivity to doxorubicin via Src-Stat3 inactivation in osteosarcoma.
abstract: Ameloblastin (AMBN), the most abundant non-amelogenin enamel matrix protein, plays a role in ameloblast differentiation. Previously, we found that AMBN promoted osteogenic differentiation via the interaction between CD63 and integrin β1, leading to the inactivation of Src; however, how AMBN affects the malignant behavior of osteosarcoma is still unclear. Osteosarcoma affects the bone and is associated with poor prognosis because of the high rate of pulmonary metastases and drug resistance. Here we demonstrated that stable overexpression of AMBN induced apoptosis and suppressed colony formation and cell migration via the inactivation of Src-Stat3 pathway in human osteosarcoma cells. Moreover, AMBN induced chemosensitivity to doxorubicin. Thus, AMBN induced a tumor suppressive phenotype and chemosensitivity to doxorubicin via the AMBN-Src-Stat3 axis in osteosarcoma. Indeed, immunohistochemical expression of AMBN was significantly correlated with better outcome of osteosarcoma patients. Our findings suggest that AMBN can be a new prognostic marker and therapeutic target for osteosarcoma combined with conventional doxorubicin treatment.
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.|Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Iizuka
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.|Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tsunematsu
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hanako
authors.initials: H
authors.lastname: Umehara
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Madhu
authors.initials: M
authors.lastname: Shrestha
authors.affiliation: Department of Orthopedic Surgery, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Orthopaedic Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Division of Orthopaedic Surgery, National Hospital Organization Kure Medical Center, Kure, Japan.
authors.forename: Shouji
authors.initials: S
authors.lastname: Shimose
authors.affiliation: Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.affiliation: Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogawa
authors.affiliation: Department of Orthopaedic Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003746:Dental Enamel Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: C490889:AMBN protein, human; D000903:Antibiotics, Antineoplastic; D003746:Dental Enamel Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004317:Doxorubicin; D015688:Oncogene Protein pp60(v-src)