A practical spatial analysis method for elucidating the biological mechanisms of cancers with abdominal dissemination in vivo

Abstract

Abstract Elucidation of spatial interactions between cancer and host cells is important for the development of new therapies against disseminated cancers. The aim of this study is to establish easy and useful method for elucidating spatial interactions. In this study, we developed a practical spatial analysis method using a gel-based embedding system and applied it to a murine model of cancer dissemination. After euthanization, every abdominal organ enclosed in the peritoneum was extracted en bloc. We injected agarose gel into the peritoneal cavities to preserve the spatial locations of the organs, including their metastatic niches, and then produced specimens when the gel had solidified. Preservation of the original spatial localization was confirmed by correlating magnetic resonance imaging results with the sectioned specimens. We examined the effects of spatial localization on cancer hypoxia using immunohistochemical hypoxia markers. Finally, we identified the mRNA expression of the specimens and demonstrated the applicability of spatial genetic analysis. In conclusion, we established a practical method for the in vivo investigation of spatial location-specific biological mechanisms in disseminated cancers. Our method can elucidate dissemination mechanisms, find therapeutic targets, and evaluate cancer therapeutic effects.