Profiling of Antibody Production against Xenograft-released Proteins by Protein Microarrays Discovers Prostate Cancer Markers

This study describes a novel xenograft-based biomarker
discovery
platform and proves its usefulness in the discovery of serum markers
for prostate cancer. By immunizing immuno-competent mice with serum
from nude mice bearing prostate cancer xenografts, an antibody response
against xenograft-derived antigens was elicited. By probing protein
microarrays with serum from immunized mice, several prostate cancer-derived
antigens were identified, of which a subset was successfully retrieved
in serum from mice bearing prostate cancer xenografts and prevalidated
in human serum samples of prostate cancer patients. Among the discovered
and validated proteins were the members of the TAM receptor family
(TYRO3, AXL, and MERTK), ACY1, and PSMA1. In conclusion, this novel
method allows for the identification of low abundant cancer-derived
serum proteins, circumventing dynamic range and host-response issues
in standard patient cohort proteomics comparisons.