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. 2019 Sep 10;10(52):5412-5418.
doi: 10.18632/oncotarget.27124.

Application of C. elegans cancer screening test for the detection of pancreatic tumor in genetically engineered mice

Yuji Ueda  1   2   3 , Koichi Kawamoto  1   2   3 , Masamitsu Konno  2   3 , Kozo Noguchi  1   2 , Satoru Kaifuchi  4 , Taroh Satoh  3 , Hidetoshi Eguchi  1 , Yuichiro Doki  1 , Takaaki Hirotsu  4   5 , Masaki Mori  1 , Hideshi Ishii  2   3
Affiliations

Application of C. elegans cancer screening test for the detection of pancreatic tumor in genetically engineered mice

Yuji Ueda et al. Oncotarget. .

Abstract

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 Kras G12D 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.

Keywords: C. elegans; early detection; genetically-engineered mice; pancreatic cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST Institutional endowments were received from Taiho Pharmaceutical Co., Ltd (Tokyo, Japan) [to Dr. H. Ishii], Evidence Based Medical Research Center INC. (Osaka, Japan) [to Dr. H. Ishii], UNITECH Co., Ltd. (Chiba, Japan) [to Dr. H. Ishii], IDEA Consultants, Inc. (Tokyo, Japan) [to Dr. H. Ishii], Kinshu-kai Medical Corporation (Osaka, Japan) [to Dr. H. Ishii], Chugai Co., Ltd. (London, UK) [to Dr. T. Satoh], Yakult Honsha Co., Ltd. [to Dr. T. Satoh], Ono Pharmaceutical Co., Ltd. (Osaka, Japan) [to Dr. T. Satoh], and Merck & Co., Ltd. (Whitehouse Station, NJ, USA) [to Dr. T. Satoh]; those sponsors had no role in the design or performance of the study, data collection, data management and interpretation, preparation of this article, or approval of the article. Drs. S. Kaifuchi and T. Hirotsu is employees of Hirotsu Bioscience Co., Ltd. (Tokyo, Japan).

Figures

Figure 1
Figure 1. HE staining for pancreatic tissue.
(A) Normal pancreatic tissue in LSL-KRASG12D negative and c-Met Wt mouse. Scale bar, 100μm; PanIN, pancreatic intraepithelial neoplasia; A, acinar cell; I, islet. (B) PanIN 2 Pancreatic Tissue in LSL-KRASG12D positive and c-Met Wt mouse. (C) Adenocarcinoma Pancreatic Tissue in LSL-KRASG12D positive and c-Met WT mouse.
Figure 2
Figure 2. Detection of tumor in mice by C. elegans scent.
(A) The method for chemotaxis assay using C. elegans. (B, C) The results for chemotaxis assay using C. elegans. Red bars mean samples were diluted at 102 before analysis. Green bars mean samples were diluted at 103 before analysis. Standard deviation was calculated using excel.
See this image and copyright information in PMC

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