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

Previously, the research group developed a novel method to detect various kinds of human cancer using nematode Caenorhabditis elegans that respond to cancer odor in urine; however, whether this method is useful for non-human species remains to be understood.

The chemotactic analysis indicated that C. elegans avoids urine of healthy recipient mice, while they tended to be attracted to urine of mice with Kras G12D. The research team's study demonstrated that C. elegans can recognize the odor of pancreatic cancer in urine of Kras G12D model mouse, suggesting the similarity of cancer odor between species.

Dr. Hideshi Ishii from the Department of Medical Data Science & the Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine at Osaka University in Osaka, Japan said, "Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and the fourth most common cause of cancer death across the world."

Thus, identification of novel biomarker for the detection of early stage of pancreatic cancer is indispensable to improve the survival of pancreatic cancer patients.

Previously, the authors found that C. elegans can detect the odor of cancer in urine of cancer patients.

Figure 1: HE staining for pancreatic tissue. (A) Normal pancreatic tissue in LSL-KRAS^G12D 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-KRAS^G12D positive and c-Met Wt mouse. (C) Adenocarcinoma Pancreatic Tissue in LSL-KRAS^G12D positive and c-Met WT mouse.

In their report, among 20 cancer patients tested, six cases were early stage cancer, suggesting that NSDT can be used for screening of early cancer.

Thus, the effectiveness of C. elegans to detect early stage of pancreatic cancer has not been fully analyzed.

Therefore, we decided to assess the possibility of NSDT to detect pancreatic tumor using mouse model.

Oncogene Kras plays a role in the generation of pancreatic cancer, and its activation is observed in >95% cases of PDAC patients.

The Ishii Research Team concluded that pancreatic development is initially associated with the activation of pancreatic and duodenal homeobox 1.

Previously, in mice bearing Pdx-1-Cre; Kras G12D; p53fl/+; Rosa YFP mutation, which develop pancreatic ductal adenocarcinoma, it was reported that pancreatic EMT and dissemination precedes pancreatic tumor formation.

Full text - https://doi.org/10.18632/oncotarget.27124

Correspondence to - Hideshi Ishii - [email protected]

Keywords - PDAC: pancreatic ductal adenocarcinoma, C.elegans: Caenorhabditis elegans