B7-H3 associated with tumor progression and epigenetic regulatory activity in cutaneous melanoma

J Invest Dermatol. 2013 Aug;133(8):2050-8. doi: 10.1038/jid.2013.114. Epub 2013 Mar 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens / genetics*
  • B7 Antigens / metabolism
  • Cell Line, Tumor
  • Disease Progression
  • Epigenesis, Genetic / physiology*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Melanoma / genetics*
  • Melanoma / secondary*
  • MicroRNAs / metabolism
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation / physiology
  • Prognosis
  • RNA, Messenger / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*

Substances

  • B7 Antigens
  • CD276 protein, human
  • MIRN29 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • STAT3 Transcription Factor
  • STAT3 protein, human