Evaluations of
tumor growth rates and molecular
biomarkers are traditionally used to assess new mouse models of human breast
cancers. This study investigated the utility of diffusion weighted (DW)-magnetic resonance imaging (MRI) for evaluating cellular proliferation of new
tumor models of
triple-negative breast cancer, which may augment traditional analysis methods. Eleven human
breast cancer cell lines were used to develop xenograft
tumors in severe combined immunodeficient mice, with two of these cell lines exhibiting sufficient growth to be serially passaged. DW-MRI was performed to measure the distributions of the apparent diffusion coefficient (ADC) in these two
tumor xenograft models, which showed a correlation with
tumor growth rates and doubling times during each passage. The distributions of the ADC values were also correlated with expression of Ki67, a
biomarker of cell proliferation, and
hypoxia inducible factor (HIF)-1α and
vascular endothelial growth factor receptor-2 (VEGFR2), which are essential
proteins involved in regulating aerobic glycolysis and angiogenesis that support
tumor cell proliferation. Although
phosphatase and
tensin homolog (PTEN) levels were different between the two xenograft models, AKT levels did not differ nor did they correlate with
tumor growth. This last result demonstrates the complexity of signaling
protein pathways and the difficulty in interpreting the effects of
protein expression on
tumor cell proliferation. In contrast, DW-MRI may be a more direct assessment of
tumor growth and
cancer cell proliferation.