The first 2 authors contributed equally to this article.
Generation and characterization of an ascitogenic mesothelin-expressing tumor model
Article first published online: 8 JUN 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 2, pages 420–431, 15 July 2007
How to Cite
Cheng, W.-F., Hung, C.-F., Chai, C.-Y., Chen, C.-A., Lee, C.-N., Su, Y.-N., Tseng, W.-Y. I., Hsieh, C.-Y., Shih, I.-M., Wang, T.-L. and Wu, T.-C. (2007), Generation and characterization of an ascitogenic mesothelin-expressing tumor model. Cancer, 110: 420–431. doi: 10.1002/cncr.22781
- Issue published online: 29 JUN 2007
- Article first published online: 8 JUN 2007
- Manuscript Accepted: 7 MAR 2007
- Manuscript Revised: 27 FEB 2007
- Manuscript Received: 29 NOV 2006
- National Science Committee of Taiwan. Grant Numbers: NSC 90-2314-B-002-157, 91-2314-B-002-315
- Alliance for Cancer Gene Therapy (ACGT)
- NCDGG. Grant Number: 1U19 CA113341-01
- tumor model;
- animal model;
- ovarian cancer
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.
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.
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.
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.