Application of C. elegans cancer screening test for the detection of pancreatic tumor in genetically engineered mice
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Yuji Ueda1,2,3, Koichi Kawamoto1,2,3, Masamitsu Konno2,3, Kozo Noguchi1,2, Satoru Kaifuchi4, Taroh Satoh3, Hidetoshi Eguchi1, Yuichiro Doki1, Takaaki Hirotsu4,5, Masaki Mori1 and Hideshi Ishii2,3
1 Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
2 Department of Medical Data Science, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
3 Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
4 Hirotsu Bioscience Co., Ltd., Tokyo 107-0062, Japan
5 Department of Biology, Graduate School of Science, Kyushu University, Fukuoka 819-0395, Japan
|Hideshi Ishii,||email:||[email protected]|
Keywords: early detection; pancreatic cancer; C. elegans; genetically-engineered mice
Abbreviations: PDAC: pancreatic ductal adenocarcinoma; C.elegans: Caenorhabditis elegans
Received: July 02, 2019 Accepted: July 17, 2019 Published: September 10, 2019
Pancreatic ductal adenocarcinoma (PDAC) exhibits a very early onset of metastasis. Thus, early detection and treatment are pivotal to successful eradication of pancreatic cancers. Economical and non-invasive cancer screening systems is indispensable for this purpose. Previously our group developed a novel method to detect various kinds of human cancer using nematode Caenorhabditis elegans (C. elegans) that respond to cancer odor in urine; however, whether this method is useful for non-human species remains to be understood. In this study, we examined its effectiveness in the detection of murine pancreatic tumor spontaneously generated in genetically-engineered mice. We generated pancreas-specific KrasG12D and/or c-Met deletion mutant mice and measured the probability of spontaneous tumor generation in these mice. The chemotactic indexes of C. elegans to the urine samples of these mutant mice were measured. As previously described, oncogenic KrasG12D was necessary to induce pancreatic intraepithelial neoplasia in this mouse model, while c-Met mutation did not show further effect. The chemotactic analysis indicated that C. elegans avoids urine of healthy recipient mice, while they tended to be attracted to urine of mice with KrasG12D. Our study demonstrated that C. elegans can recognize the odor of pancreatic cancer in urine of KrasG12D model mouse, suggesting the similarity of cancer odor between species. Our result facilitates further studies on mechanism of cancer detection by C. elegans.
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