A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma

Our plain-English summary of A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma, by S.M. Lansley, J.F. Varano Della Vergiliana, A.L. Cleaver, et al (Respirology, 2014).

The study

• Authors: S.M. Lansley, J.F. Varano Della Vergiliana, A.L. Cleaver, S.H. Ren, A. Segal, M.Y. Xu, Y.C. Lee
• Journal: Respirology
• Published: 2014;19(7):1025-33
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background And Objective: Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has anti-tumoural activities against pleural malignancies, in addition to its pleurodesing effect.

Methods: The effects of the treatment on mesothelioma cells were evaluated in vitro and further tested in two validated murine models.

Results: This S. aureus bio-product mixture effectively kills mesothelioma cells and induces the release of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and vascular endothelial growth factor from primary human mesothelial cells but not malignant pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in BALB/c mice induced tumour necrosis and local activation of T cells. Tumour growth was significantly inhibited in the treatment group during and after the treatment period (size of tumour 58.8 ± 10.3 mm(2) vs 118.3 ± 6.7 mm(2) from saline controls at day 23, n = 9-12 per group), P < 0.001. Tumour growth resumed on cessation of treatment, confirming the inhibition was treatment related. Treatment benefits were further validated in an orthotopic peritoneal model of mesothelioma and the compound significantly reduced the mesothelioma load (P < 0.05 vs saline controls). Mice in the treatment group had a significant increase in the percentage of activated CD4(+) and CD8(+) T cells in tumour-draining lymph nodes. No histological side-effects were observed with the treatment.

Conclusions: This proof-of-principle study demonstrates promising antitumoural activity of a commercially available compound of S. aureus bio-products against mesothelioma.

© 2014 Asian Pacific Society of Respirology.

In plain English

This laboratory study tested Enge Fei, a commercially available mixture of Staphylococcus aureus bio-products, against mesothelioma cells grown in dishes and in mice. It did not study asbestos exposure. In mice with flank mesothelioma tumours, six daily injections of the mixture into the tumour were followed by smaller tumours than saline injections: 58.8 ± 10.3 mm2 versus 118.3 ± 6.7 mm2 at day 23 (P less than 0.001). Treated tumours took about 5 days longer to reach the 100 mm2 end-point, and they started growing again when treatment stopped. In a peritoneal (abdominal cavity) mesothelioma model, treated mice had a smaller tumour burden (P less than 0.05). Treated flank tumours showed about three-fold more necrosis (tissue death), and activated T cells increased in nearby lymph nodes. Weights did not differ significantly, and no treatment-related tissue changes were seen in examined organs, including liver, kidneys and lungs. In dishes, the mixture reduced survival of all three human mesothelioma cell lines and two of four mouse lines, but not benign mesothelial cells. The authors concluded that clinical evaluation of the compound against mesothelioma is warranted.

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: Proof-of-concept laboratory study: in vitro cell experiments plus animal experiments in two mouse models of mesothelioma (flank tumour model and orthotopic peritoneal model)
• Who was studied: BALB/c mice implanted with AB1-HA mesothelioma cells (flank model: 12 treated and 9 saline mice per the Methods; peritoneal model also used). In vitro: seven mesothelioma cell lines (three human: LO68, JU77, CRL-2081; four mouse: AE5, AE17, AB1-HA, AB2/AB22) and three benign mesothelial cell lines (primary human mesothelial cells from pericardial fluid of two patients, and the Met5A line). Work was done at the University of Western Australia.
• Exposure: Not an asbestos exposure study. The exposure was a treatment: Enge Fei, a commercial Staphylococcus aureus bio-product mixture (metabolites including enterotoxin C). Flank model: 2 ng in 200 μL saline injected into the tumour daily for 6 days from day 10, compared with saline. Peritoneal model: mixture or saline injected into the abdominal cavity daily for 6 days from day 7. In vitro doses: 0 to 5 ng/mL.
• Main results:
  • Flank model: tumours were significantly smaller in treated mice than in saline controls at 23 days after tumour inoculation (58.8 ± 10.3 mm2 vs 118.3 ± 6.7 mm2; P < 0.001).
  • Flank model: treated tumours took about 5 days longer than controls to reach the 100 mm2 size cut-off (P < 0.001).
  • Flank model: tumour growth resumed after the injections stopped.
  • Peritoneal model: treated mice had significantly reduced tumour burden (number of tumour nodules) compared with saline controls (P < 0.05).
  • No significant difference in body weight between treated and control mice throughout the experimental period.
  • No tissue architectural or pathological/histological changes attributable to the treatment were observed in the organs examined, including the liver, kidneys and lungs.
  • Tumours from treated mice showed approximately three-fold more extensive necrosis than tumours from control mice (P < 0.05; 7 treated vs 6 saline mice).
  • Activation of CD4+ and CD8+ T cells was significantly increased (by three-fold and two-fold) in the tumour-draining lymph nodes of treated mice, but not in non-draining lymph nodes or the spleen (6 treated vs 4 saline mice).
  • In vitro: the mixture decreased cell viability in all human mesothelioma cell lines but not in benign mesothelial cells.
  • In vitro: apoptosis increased in the human mesothelioma lines at higher doses (CRL-2081: 1.88 ± 0.20-fold, JU77: 1.31 ± 0.09-fold, LO68: 1.81 ± 0.18-fold over controls).
  • In vitro: two of the four mouse mesothelioma lines (AB1-HA, 1.44 ± 0.05-fold; AB22, 1.34 ± 0.03-fold) were susceptible to treatment-induced apoptosis. AE5 and AE17 were not affected.
  • In vitro: IL-8 release increased significantly in all three human benign mesothelial cell lines after treatment. There was no significant change in IL-8, MCP-1 or VEGF release from the mesothelioma cell lines.
• The authors' conclusion: The authors concluded that this S. aureus bio-product mixture was efficacious against mesothelioma in vitro and significantly inhibited tumour growth in mice, and that clinical evaluation of the compound against mesothelioma is warranted.
• Limitations the authors state:
  • The mechanism by which the mixture inhibited tumour growth was not further explored.
  • Pharmacokinetics with systemic delivery and efficacy in pleural models of mesothelioma were not studied and remain for future work.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleurodesis, Mesothelial Cells, Pleural Mesothelioma, Necrosis.

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• The role of the receptor for advanced glycation end-products in a murine model of silicosis — L. Ramsgaard, J.M. Englert, et al. (2010)
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• Establishment of a murine model of malignant mesothelioma — M.R. Davis, L.S. Manning, et al. (1992)

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