Generation and characterization of an ascitogenic mesothelin-expressing tumor model

Authors

  • Wen-Fang Cheng MD, PhD,

    1. Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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    • The first 2 authors contributed equally to this article.

  • Chien-Fu Hung PhD,

    1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
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    • The first 2 authors contributed equally to this article.

  • Chee-Yin Chai MD, PhD,

    1. Department of Pathology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Chi-An Chen MD,

    1. Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Chien-Nan Lee MD,

    1. Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Yi-Ning Su MD, PhD,

    1. Department of Genetic Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Wen-Yih Isaac Tseng MD, PhD,

    1. Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Chang-Yao Hsieh MD,

    Corresponding author
    1. Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    • Department of Pathology, School of Medicine, Johns Hopkins University, CRBII Rm. 309, 1550 Orleans St., Baltimore, MD 21231
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    • Fax: (011) 886-2-2395-9476

  • Ie-Ming Shih MD, PhD,

    1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    3. Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Tian-Li Wang PhD,

    1. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • T.-C. Wu MD, PhD

    Corresponding author
    1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    3. Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    4. Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    • Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
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    • Fax: (443) 287-4295


Abstract

BACKGROUND.

Intraperitoneal tumors expressing high amounts of mesothelin such as malignant mesothelioma and ovarian cancers tend to develop ascites and result in significant morbidity and mortality in the patient. A suitable preclinical intraperitoneal model will assist in the illustration of the mechanisms of molecular oncogenesis and facilitate in addressing issues related to early screening, diagnosis, and therapy for intraperitoneal tumors.

METHODS.

In the current study, an ascitogenic malignant tumor model (WF-3) was created. The mobility and proliferation of WF-3 and its precursor cells, WF-0, were characterized using transwell and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. In addition, the in vivo tumorgenicity of WF-3 and WF-0 was determined using intraperitoneal injection of the tumor cells. Microarray analysis was performed using WF-3 and WF-0. Northern blot analysis was used to characterize the expression of the mesothelin gene in WF-3 and WF-0. Furthermore, the mesothelin levels in serum and ascites were used to correlate with tumor load of WF-3 in tumor challenged mice.

RESULTS.

The WF-3 tumor cells demonstrated relatively high proliferation and migration rates compared with the parental cell line, WF-0. The tumors from the WF-3 but not WF-0 were capable of forming ascites and peritoneal-based tumors after tumor challenge. The WF-3 tumor model was also capable of implanting into multiple organs including the diaphragm, intestines, and peritoneal wall. Furthermore, the WF-3 tumor expressed high levels of mesothelin, which is commonly observed in the majority of ovarian cancers, pancreatic cancer, and malignant mesothelioma. In addition, the authors found that the serum and ascites mesothelin levels correlated with tumor loads in tumor-challenged mice.

CONCLUSIONS.

The data indicate that the WF-3 murine tumor model may potentially serve as a good model for understanding the molecular oncogenesis of peritoneal tumors. In addition, the preclinical model may potentially be useful for the development of diagnostic and therapeutic methods against intraperitoneal cancers. Cancer 2007. © 2007 American Cancer Society.

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