Low-volume, high-throughput sandwich immunoassays for profiling plasma proteins in mice: identification of early-stage systemic inflammation in a mouse model of intestinal cancer.
Mouse models of human cancers may provide a valuable resource for the discovery of cancer biomarkers. We have developed a practical strategy for profiling specific proteins in mouse plasma using low-volume sandwich-immunoassays. We used this method to profile the levels of 14 different cytokines, acute-phase reactants, and other cancer markers in plasma from a mouse models of intestinal tumors and their wild-type littermates, using as little as 1.5 microliters of diluted plasma per assay. Many of the proteins were significantly and consistently up-regulated in the mutant mice. The mutant mice could be distinguished nearly perfectly from the wild-type mice based on the combined levels of as few as three markers. Many of the proteins were up-regulated even in the mutant mice with few or no tumors, suggesting the presence of a systemic host response at an early stage of cancer development. These results have implications for the study of host responses in mouse models of cancers and demonstrate the value of a new low-volume, high-throughput sandwich-immunoassay method for sensitively profiling protein levels in cancer.
Forrester
Sara
S
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Hung
Kenneth E
KE
Kuick
Rork
R
Kucherlapati
Raju
R
Haab
Brian B
BB
D000209:Acute-Phase Proteins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000097:blood; D007414:Intestinal Neoplasms / Q000097:blood*; D051379:Mice; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins / Q000032:analysis / Q000097:blood*; D009374:Neoplasms, Experimental / Q000097:blood; D040081:Protein Array Analysis / Q000295:instrumentation / Q000379:methods*; D012680:Sensitivity and Specificity
D000209:Acute-Phase Proteins; D016207:Cytokines; D009363:Neoplasm Proteins