Rapid protein display profiling of cancer progression directly from human tissue using a protein biochip

Cloud P. Paweletz, John W. Gillespie, David K. Ornstein, Nicole L. Simone, Monica R. Brown, Kristina A. Cole, Quan Hong Wang, Jing Huang, Nan Hu, Tai Tung Yip, William E. Rich, Elise C. Kohn, W. Marston Linehan, Thomas Weber, Phil Taylor, Mike R. Emmert-Buck, Lance A. Liotta, Emanuel F. Petricoin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

The complicated, changing pattern of protein expression should contain important information about the pathologic process taking place in the cells of actual tissue. Utilization of this information for the selection of druggable targets could be possible if a means existed to rapidly analyze and display changes in protein expression in defined microscopic cellular subpopulations. As a demonstration of feasibility, we show the generation of sensitive, rapid, and reproducible molecular weight protein profiles of patient-matched normal, premalignant, malignant, and metastatic microdissected cell populations from stained human esophageal, prostate, breast, ovary, colon, and hepatic tissue sections through the application of an affinity-based biochip. Reproducible, discriminatory protein biomarker profiles can be obtained from as few as 25 cells in less than 5 min from dissection to the generation of the protein fingerprint. Furthermore, these protein pattern profiles reveal reproducible changes in expression as cells undergo malignant transformation, and are discriminatory for different tumor types. Consistent protein changes were identified in the microdissected cells from patient-matched tumor and normal epithelium from eight out of eight different malignant esophageal tissue sets and three out of three malignant prostate tissue sets. A means to rapidly generate a display of expressed proteins from microscopic cellular populations sampled from tissue could be an important enabling technology for pharmacoproteomics, molecular pathology, drug intervention strategies, therapeutic assessment of drug entities, disease diagnosis, toxicity, and gene therapy monitoring. Published 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalDrug Development Research
Volume49
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Biomarker
  • Laser
  • Mass spectrometry
  • Microdissection
  • Pharmacog enomics
  • Pharmacoproteomics
  • Proteomics
  • SELDI

Fingerprint

Dive into the research topics of 'Rapid protein display profiling of cancer progression directly from human tissue using a protein biochip'. Together they form a unique fingerprint.

Cite this