Cancer type-specific tNOX isoforms: A putative family of redox protein splice variants with cancer diagnostic and prognostic potential

Biofactors. 2008;34(3):201-7. doi: 10.3233/BIO-2009-1073.

Abstract

A proteomics approach with detection on western blots using an S-peptide tagged pan-tNOX (ENOX2) recombinant (scFv) antibody followed by alkaline phosphatase-linked anti S has revealed a family of more than 20 ENOX2 isoforms of varying molecular weights (34 to 94 kDa) and mostly of low isoelectric points (4.6 +/- 0.7) based on serum analysis. Different isoforms characterize cancers of different tissue origins indicative of both cancer presence and tissue site of origin. ENOX2 proteins are cancer-associated and differ from constitutive (CNOX or ENOX1) proteins primarily by the absence of a drug binding site to which the cancer-specific scFv is directed. All are located on the cell surface where they function both as terminal oxidases for plasma membrane electron transport and carry out protein disulfide-thiol interchange. These proteins are shed into the blood and can also be found in urine. The tNOX isoform technology is under development as a clinical aid to identify unknown or uncertain primary cancers, evaluation of metastatic spread in post surgery patients, monitoring remission following cessation of therapy and for early diagnosis in at-risk populations.

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / metabolism
  • Colonic Neoplasms / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Humans
  • Lung Neoplasms / metabolism
  • Lymphoma, Non-Hodgkin / metabolism
  • Male
  • Melanoma / metabolism
  • NADH, NADPH Oxidoreductases / analysis*
  • NADH, NADPH Oxidoreductases / genetics
  • NADH, NADPH Oxidoreductases / metabolism*
  • Neoplasms / metabolism*
  • Ovarian Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Prostatic Neoplasms / metabolism
  • Protein Isoforms / analysis*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Uterine Cervical Neoplasms

Substances

  • Protein Isoforms
  • NADH, NADPH Oxidoreductases
  • tumor-associated NADH oxidase