Novel surface targets and serum biomarkers from the ovarian cancer vasculature

Cancer Biol Ther. 2011 Aug 1;12(3):169-80. doi: 10.4161/cbt.12.3.16260. Epub 2011 Aug 1.

Abstract

The molecular phenotype of tumor vasculature is different from normal vasculature, offering new opportunities for diagnosis and therapy of cancer, but the identification of tumor-restricted targets remains a challenge. We investigated 13 tumor vascular markers (TVMs) from 50 candidates identified through expression profiling of ovarian cancer vascular cells and selected to be either transmembrane or secreted, and to be either absent or expressed at low levels in normal tissues while overexpressed in tumors, based on analysis of 1,110 normal and tumor tissues from publicly available Affymetrix microarray data. Tumor-specific expression of each TVM was confirmed at the protein level in tumor tissue and/or in serum. Among the 13 TVMs, 11 were expressed on tumor vascular endothelium; the remaining 2 TVMs were expressed by tumor leukocytes. Our results demonstrate that certain transmembrane TVMs such as ADAM12 and CDCP1 are selectively expressed in tumor vasculature and represent promising targets for vascular imaging or anti-vascular therapy of epithelial ovarian cancer, while secreted or shed molecules such as TNFRSF21/DR6 can function as serum biomarkers. We have identified novel tumor-specific vasculature markers which appear promising for cancer serum diagnostics, molecular imaging and/or therapeutic targeting applications and warrant further clinical development.

Publication types

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

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • ADAM12 Protein
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Ovarian Epithelial
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Hypoxia / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms, Glandular and Epithelial / blood supply
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Receptors, Tumor Necrosis Factor / blood
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDCP1 protein, human
  • Cell Adhesion Molecules
  • Membrane Proteins
  • Neoplasm Proteins
  • Receptors, Tumor Necrosis Factor
  • TNFRSF21 protein, human
  • ADAM Proteins
  • ADAM12 Protein
  • ADAM12 protein, human