Expression of angiogenic factors Cyr61 and tissue factor in uveal melanoma

Arch Ophthalmol. 2002 Dec;120(12):1719-25. doi: 10.1001/archopht.120.12.1719.

Abstract

Objective: To study the expression of angiogenic factors Cyr61 and tissue factor (TF) in uveal melanoma and its correlation with blood vessel density.

Methods: Suppression subtractive hybridization was used to identify genes that are differentially expressed between cell lines of uveal melanoma and normal uveal melanocytes. Expression of these genes was subsequently verified in primary uveal melanomas and correlated with the number of blood vessels in archival specimens by immunohistochemical analysis.

Results: Cyr61 and TF are expressed at elevated levels in cell lines of uveal melanoma compared with normal uveal melanocytes. Duplication of a region of chromosome arm 1p, encompassing the genes encoding Cyr61 and TF, was observed in the melanoma cell line used in the initial subtractive hybridization. Both genes are also expressed in primary uveal melanomas, and a correlation was found between expression of TF and the number of blood vessels in archival specimens.

Conclusions: Cyr61 and TF may contribute to the angiogenic phenotype associated with uveal melanoma. A region of chromosome arm 1p also may contain oncogenes or tumor suppressor genes pertinent to the origins of this type of ocular tumor.

Clinical relevance: New immunotherapies have been devised for the treatment of cancer based on the expression of TF. Similar approaches may be effective in treating uveal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Chromosomes, Human, Pair 1 / genetics
  • Cysteine-Rich Protein 61
  • Cytogenetics
  • Endothelial Growth Factors / metabolism
  • Humans
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphokines / metabolism
  • Melanoma / blood supply
  • Melanoma / metabolism*
  • Neovascularization, Pathologic / pathology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thromboplastin / genetics*
  • Thromboplastin / metabolism
  • Tumor Cells, Cultured
  • Uveal Neoplasms / blood supply
  • Uveal Neoplasms / metabolism*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • CCN1 protein, human
  • Cysteine-Rich Protein 61
  • Endothelial Growth Factors
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Thromboplastin