In vivo imaging of human malignant mesothelioma grown orthotopically in the peritoneal cavity of nude mice

Our plain-English summary of In vivo imaging of human malignant mesothelioma grown orthotopically in the peritoneal cavity of nude mice, by M. Feng, J. Zhang, M. Anver, et al (Journal of Cancer, 2011).

The study

• Authors: M. Feng, J. Zhang, M. Anver, R. Hassan, M. Ho
• Journal: Journal of Cancer
• Published: 2011;2:123-31
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP) fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL) that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo.

In plain English

This laboratory and animal study described the construction of a mouse model of human malignant mesothelioma. The authors labelled the human mesothelioma cell line NCI-H226 with a lentiviral vector carrying a luciferase-GFP fusion gene and, after flow-cytometry sorting and single-cell cloning, selected a clone named LMB-H226-GL. In culture, mesothelin expression did not differ between the parental and labelled cells, and the IC50 for the anti-mesothelin immunotoxin SS1P was 0.6 ng/mL for LMB-H226-GL and 0.4 ng/mL for NCI-H226. Female athymic nude mice received 10 million (high-dosage) or 5 million (low-dosage) cells intraperitoneally; tumours formed in the peritoneum and were followed by bioluminescence imaging, with photon intensity correlating better with tumour weight (0.77) than size (0.57). At necropsy, white tumours were attached to and sometimes invaded the peritoneal wall, and similar masses lay on the visceral peritoneum of the pancreas, liver, diaphragm and gonadal fat pads, staining for mesothelin and GFP. SS1P at 0.4 mg/kg, started on day 1 or day 9, lowered bioluminescence significantly versus control (p less than 0.05) but did not eradicate tumours. The authors concluded the model is well suited for evaluating anti-mesothelioma agents.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory cell-line engineering plus animal (nude mouse) xenograft experiment with in vivo imaging and immunotoxin treatment
• Who was studied: Human mesothelioma cell line NCI-H226 (from ATCC) and six-week-old female athymic nude mice (NCr-nu/nu) from NCI-Frederick; treatment experiment used two treatment groups and one control group of eight mice each
• Exposure: Intraperitoneal injection of 5 or 10 million Luc/GFP-labelled LMB-H226-GL mesothelioma cells; treatment with the anti-mesothelin recombinant immunotoxin SS1P at 0.4 mg/kg intraperitoneally
• Main results:
  • No difference in mesothelin expression between parental and labelled cells; SS1P IC50 was 0.6 ng/mL for LMB-H226-GL and 0.4 ng/mL for NCI-H226
  • Tumour growth rate in the high-dosage group was similar to the low-dosage group, with relatively larger tumours in the high-dosage group
  • Bioluminescence correlated more strongly with tumour weight than with tumour size in the injected mice
  • At necropsy, tumours were attached to and sometimes invaded the peritoneal wall, with similar masses on the visceral peritoneum of pancreas, liver, diaphragm and gonadal fat pads
  • Bioluminescence fell in both SS1P treatment groups two days after the first injection, with a significant difference versus control
  • In the subset of mice whose lungs were examined, 2/4 control mice and 0/6 treated mice had mesothelioma micrometastases
  • At the end of the study (day 60 high-dosage, day 67 low-dosage) most mice were thin, sick and less active; one mouse had a distended abdomen but no ascites was found
• The authors' conclusion: The authors concluded that the LMB-H226-GL peritoneal model is well suited for mesothelioma and may be useful for evaluating novel agents in vivo, and that it offers an improved method for evaluating anti-mesothelioma therapeutics compared with subcutaneous models
• Limitations the authors state:
  • SS1P treatment did not completely eradicate tumour cells, and the authors' speculation of acquired drug resistance was not supported by in vitro testing of surviving cells (data not shown)
  • Histopathological examination of lungs was done only in a subset of mice

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Peritoneal Cavity, Peritoneum, Clinical Trial.

Related studies

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• The therapeutic efficacy of S-1 against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice — T.T. Van, M. Hanibuchi, et al. (2011)
• Effects of photodynamic therapy on xenografts of human mesothelioma and rat mammary carcinoma in nude mice — S.L. Gibson, T.H. Foster, et al. (1994)
• Effects of natural interferon alpha, natural tumor necrosis factor alpha and their combination on human mesothelioma xenografts in nude mice — T. Ohnuma, L. Szrajer, et al. (1993)
• Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models — E. Inamasu, T. Tsuchiya, et al. (2022)

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