Ultrasound imaging of splenomegaly as a proxy to monitor colon tumor development in Apcmin716/+ mice

Abstract

Animal models of colon cancer are widely used to understand the molecular mechanisms and pathogenesis of the disease. These animal models require a substantial investment of time and traditionally necessitate the killing of the animal to measure the tumor progression. Several in vivo imaging techniques are being used in both human clinics and preclinical studies, albeit at high cost and requiring particular expertise. Here, we report that the progression of splenomegaly coincides with and positively correlates to colon tumor development in Apc^min716/+ mice expressing a mutant gene encoding an adenomatous polyposis coli protein truncated at amino acid 716. Ultrasound image-based spleen size measurement precisely mirrors splenomegaly development in vivo in the tumor-laden Apc^min716/+ mice. Moreover, the spleen dimensions extracted from the ultrasound sonograms are positively correlated with normalized spleen weight and the number and area of colon tumors. Hence, we propose measuring the spleen size in vivo by ultrasound imaging as a novel approach to estimate splenomegaly development and to indirectly monitor colon tumor development in Apc^min716/+ mice. The widespread use of ultrasound machines in the laboratory setting, coupled with the fact that it is a noninvasive method, make it a straightforward and useful tool for monitoring the experimental progress of colon cancer in mice and determining end points without killing animals strictly for diagnostics purposes.

The relationship between colon tumorigenesis and splenomegaly in Apc^Min/+ mice has not been investigated. We demonstrate that splenomegaly progression coincides with and positively correlates to colon tumor development in Apc^min716/+ mice and ultrasound image-based spleen measurement precisely monitors splenomegaly development in vivo. These findings reveal measuring the spleen size in vivo by ultrasound imaging is a novel noninvasive approach to estimate splenomegaly development as an indirect monitoring tool for colon tumor development in Apc^min716/+ mice.

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