title: B7-H3 associated with tumor progression and epigenetic regulatory activity in cutaneous melanoma.
abstract: B7-H3, a cell surface transmembrane glycoprotein, was assessed for its functional and prognostic role in cutaneous melanoma progression. B7-H3 expression in melanoma cells was shown to be related to specific downstream signal transduction events as well as associated with functional epigenetic activity. B7-H3 expression and prognostic utility were shown by reverse transcription and real-time PCR and immunohistochemistry analysis on individual melanoma specimens and then verified in clinically annotated melanoma stage III and stage IV metastasis tissue microarrays in a double-blind study. B7-H3 messenger RNA expression was shown to be significantly increased with stage of melanoma (P<0.0001) and significantly associated with melanoma-specific survival in both stage III (P<0.0001) and stage IV (P<0.012) melanoma patients. B7-H3 expression was related to migration and invasion; overexpression of B7-H3 increased migration and invasion, whereas knockdown of B7-H3 reduced cell migration and invasion. MiR-29c expression was shown to inversely regulate B7-H3 expression. Furthermore, we demonstrated that melanoma B7-H3 expression was correlated to phosphorylated signal transducer and activator of transcription-3 activity level in melanoma tissues and cell lines. These studies demonstrate that B7-H3 is a significant factor in melanoma progression and events of metastasis.
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute (JWCI), Santa Monica, California 90404, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Chong
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Linhda
authors.initials: L
authors.lastname: Nguyen
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Huang
authors.forename: Christine
authors.initials: C
authors.lastname: Kuo
authors.forename: Wang
authors.initials: W
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
mesh_terms: D060887:B7 Antigens / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000556:secondary*; D035683:MicroRNAs / Q000378:metabolism; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000502:physiology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human