Serial analysis of 38 proteins during the progression of human breast tumor in mice using an antibody colocalization microarray.
Bottom Line: The profiles of 38 proteins detected in sera from these animals were analyzed by clustering, and we identified 10 proteins with the greatest relative increase in serum concentration that correlated with growth of the primary mammary tumor.Next, the sensitivity and specificity of individual and optimal protein panels were calculated, showing high accuracy as early as week 2.These results provide a foundation for studies of tumor growth through measuring serial changes of protein concentration in animal models.
Affiliation: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre.Show MeSH
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Mentions: The time course of tumor growth is shown in Fig. 3, top left panel. The results show important variations from animal to animal. Although variability in tumor growth is generally known, it should be noted that all cancers originated from a cell line with reduced genetic variability compared with natural tumors and were implanted in mice with similar genetic background, and yet widely varying growth rates and final tumor volumes are observed despite the homogeneous genetic background. To further investigate the 10 increased proteins found in Fig. 2, we plotted their concentrations during tumor growth for both individual mice and the average of all tumor-bearing and control mice. Six proteins (G-CSF, IL-8, TNF-RI, uPA, uPAR, and GM-CSF) increased continuously during the growth of human xenografts with only small fluctuations, and the remaining four proteins (EGFR, CEA, MMP-3, and FAS) also increased but with significant fluctuation (Fig. 3). EGFR shows relatively high signals in control mice, which might be due to the cross-reactivity of antibodies with other antigens (20). Regardless, on average, a clear trend is visible for EGFR as the signal rises significantly. The fluctuation in protein concentrations in samples taken prior to cancer cell injection (week −1 and week 0) and of control animals might be ascribed to the variability in sample collection and serum and the specificity of the antibodies. The correlation between tumor size and protein concentration was not consistent among mice. Mice M3456 and M3464 grew large tumors, and the concentration of proteins in blood was also high in relation to the other mice. However, M3460 shows a moderately sized tumor but high concentrations of proteins in the blood, indicating that the correlation between protein concentration and tumor size is not consistent among different mice as will be further discussed below.
Affiliation: From the ‡Biomedical Engineering Department, §McGill University and Genome Quebec Innovation Centre.