Rat N-ERC/mesothelin as a marker for in vivo screening of drugs against pancreas cancer

Katsumi Fukamachi; Masaaki Iigo; Yoshiaki Hagiwara; Koji Shibata; Mitsuru Futakuchi; David B Alexander; Okio Hino; Masumi Suzui; Hiroyuki Tsuda

doi:10.1371/journal.pone.0111481

Rat N-ERC/mesothelin as a marker for in vivo screening of drugs against pancreas cancer

PLoS One. 2014 Oct 27;9(10):e111481. doi: 10.1371/journal.pone.0111481. eCollection 2014.

Authors

Katsumi Fukamachi¹, Masaaki Iigo², Yoshiaki Hagiwara³, Koji Shibata⁴, Mitsuru Futakuchi¹, David B Alexander², Okio Hino⁵, Masumi Suzui¹, Hiroyuki Tsuda²

Affiliations

¹ Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
² Nanotoxicology Project, Nagoya City University, Nagoya, Japan.
³ Immuno-Biological Laboratories, Fujioka-shi, Gunma, Japan.
⁴ Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵ Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease, which is usually diagnosed in an advanced stage. We have established transgenic rats carrying a mutated K-ras gene controlled by Cre/loxP activation. The animals develop PDA which is histopathologically similar to that in humans. Previously, we reported that serum levels of N-ERC/mesothelin were significantly higher in rats bearing PDA than in controls. In the present study, to determine whether serum levels of N-ERC/mesothelin correlated with tumor size, we measured N-ERC/mesothelin levels in rats bearing PDA. Increased serum levels of N-ERC/mesothelin correlated with increased tumor size. This result indicates an interrelationship between the serum level of N-ERC/mesothelin and tumor size. We next investigated the effect of chemotherapy on serum N-ERC/mesothelin levels. Rat pancreatic cancer cells were implanted subcutaneously into the flank of NOD-SCID mice. In the mice treated with 200 mg/kg gemcitabine, tumor weight and the serum level of N-ERC/mesothelin were significantly decreased compared to controls. These results suggest that serum N-ERC/mesothelin measurements might be useful for monitoring response to therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / blood*
Adenocarcinoma / drug therapy
Animals
Antineoplastic Agents / therapeutic use*
Biomarkers, Tumor / blood*
Deoxycytidine / analogs & derivatives*
Deoxycytidine / therapeutic use
Drug Evaluation, Preclinical / methods
Female
GPI-Linked Proteins / blood*
Gemcitabine
Male
Mesothelin
Mice
Mice, Inbred NOD
Mice, SCID
Pancreatic Neoplasms / blood*
Pancreatic Neoplasms / drug therapy
Rats
Rats, Sprague-Dawley
Rats, Wistar

Substances

Antineoplastic Agents
Biomarkers, Tumor
GPI-Linked Proteins
Msln protein, mouse
Msln protein, rat
Deoxycytidine
Mesothelin
Gemcitabine

Grants and funding

This work was supported in part by Adaptable and Seamless Technology transfer Program through target-driven R&D (A-STEP) from Japan Science and Technology Agency; a Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science; a Grant-in-Aid for Research in Nagoya City University; the Aichi Cancer Research Foundation; the Program for developing the supporting system for upgrading the education and research from the Ministry of Education, Culture, Sports, Science and Technology; and a Grant-in-Aid for Cancer Research (17S-6, 20S-8) from the Ministry of Health, Labour and Welfare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.