Cross-Species Proteomics Identifies CAPG and SBP1 as Crucial Invasiveness Biomarkers in Rat and Human Malignant Mesothelioma

Our plain-English summary of Cross-Species Proteomics Identifies CAPG and SBP1 as Crucial Invasiveness Biomarkers in Rat and Human Malignant Mesothelioma, by J.S. Nader, A. Boissard, C. Henry, et al (Cancers, 2020).

The study

• Authors: J.S. Nader, A. Boissard, C. Henry, I. Valo, V. Verrièle, M. Grégoire, O. Coqueret, C. Guette, D.L. Pouliquen
• Journal: Cancers
• Published: 2020;12(9)
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) still represents a devastating disease that is often detected too late, while the current effect of therapies on patient outcomes remains unsatisfactory. Invasiveness biomarkers may contribute to improving early diagnosis, prognosis, and treatment for patients, a task that could benefit from the development of high-throughput proteomics. To limit potential sources of bias when identifying such biomarkers, we conducted cross-species proteomic analyzes on three different MM sources. Data were collected firstly from two human MM cell lines, secondly from rat MM tumors of increasing invasiveness grown in immunocompetent rats and human MM tumors grown in immunodeficient mice, and thirdly from paraffin-embedded sections of patient MM tumors of the epithelioid and sarcomatoid subtypes. Our investigations identified three major invasiveness biomarkers common to the three tumor sources, CAPG, FABP4, and LAMB2, and an additional set of 25 candidate biomarkers shared by rat and patient tumors. Comparing the data to proteomic analyzes of preneoplastic and neoplastic rat mesothelial cell lines revealed the additional role of SBP1 in the carcinogenic process. These observations could provide new opportunities to identify highly vulnerable MM patients with poor survival outcomes, thereby improving the success of current and future therapeutic strategies.

In plain English

This laboratory study used mass spectrometry (SWATH-MS) to look for proteins linked to how invasive malignant mesothelioma tumors are. It did not study asbestos exposure. The authors compared three sources. The first was four rat mesothelioma tumor models of differing invasiveness grown in rats. The second was two human mesothelioma cell lines (Meso 34 and Meso 163) and tumors grown from them in immunodeficient mice. The third was pleural mesothelioma tissue from four patients, two sarcomatoid and two epithelioid. The three tumor comparisons found 433, 133 and 191 proteins whose levels differed significantly. Three proteins, CAPG, FABP4 and LAMB2, changed in all three tumor sources. CAPG was increased, and it was the only one of the three with a statistically significant matching change in the human cell lines; LAMB2 showed a similar but non-significant tendency. Another 25 candidate proteins were shared by rat and patient tumors. In rat mesothelial cell lines, one of these, SBP1, decreased continuously from preneoplastic to neoplastic cells. The authors stated the study was limited by its small number of samples and called for larger studies.

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 proteomic study comparing protein levels across rat tumor models, human cell lines and xenografts in mice, and patient tumor samples (cross-species comparison)
• Who was studied: Four rat malignant mesothelioma tumor models (M5-T2 noninvasive; F4-T2, F5-T1, M5-T1 invasive) grown in syngeneic rats; two human MM cell lines (Meso 34, Meso 163) from pleural effusions of patients with suspected pleural MM, also grown as tumors in two groups of five NOD SCID mice; paraffin-embedded pleural MM tumor pieces from four patients (two sarcomatoid, two epithelioid) from the Reims University Hospital tumor bank, France; and a collection of 27 rat mesothelial cell lines (preneoplastic and neoplastic)
• Exposure: No asbestos or fiber exposure was studied; the comparisons were between more invasive and less invasive tumors (and between sarcomatoid and epithelioid patient tumors)
• Main results:
  • The number of proteins with a fold change greater than 1.5 and p less than 0.05 was 433 (invasive vs noninvasive rat tumors), 133 (Meso 163 vs Meso 34 xenografts in mice) and 191 (sarcomatoid vs epithelioid patient tumors)
  • Three proteins, CAPG, FABP4 and LAMB2, showed common changes in all three tumor sources
  • CAPG was increased in human MM cell lines, human MM tumor models and patient MM
  • LAMB2 showed decreased abundance in all tumor sources
  • In the Meso 163 vs Meso 34 human cell line comparison, CAPG was the only one of the three proteins with a statistically significant similar change. LAMB2 showed a strong tendency (p between 0.05 and 0.09, not statistically significant), and FABP4 showed no significant change.
  • A further 25 candidate proteins were shared by rat and patient MM tumors
  • In rat mesothelial cell lines, SBP1 was the only one of six proteins with a continuous decrease from preneoplastic subgroups with epithelioid morphology to sarcomatoid subgroups, with a further decrease in neoplastic cell lines
  • SBP1 was also decreased in association with increased invasiveness in human cell lines and in rat and patient MM tumors
• The authors' conclusion: The authors concluded that some proteins showed the same patterns of change in mesothelioma cells and tumors from different sources and two species. They suggested that SBP1 is of additional interest as a biomarker of neoplastic transformation, and that the work should be extended to more samples.
• Limitations the authors state:
  • The study was limited by the small number of samples
  • The authors noted that tumors transplanted into immunodeficient mice are less relevant for stromal and vascular interactions than tumors grown in syngeneic animals

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Prognosis, Epithelioid, Sarcomatoid, Mesothelial Cells, Carcinogenic.

Related studies

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• Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells-Potential Links with Sarcomas — D.L. Pouliquen, A. Boissard, et al. (2020)
• A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma — S.C. Kao, M.B. Kirschner, et al. (2016)
• Long-Chain Acyl Coenzyme A Dehydrogenase, a Key Player in Metabolic Rewiring/Invasiveness in Experimental Tumors and Human Mesothelioma Cell Lines — D.L. Pouliquen, G. Ortone, et al. (2023)
• S100A4 is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma — J.S. Nader, J. Guillon, et al. (2020)
• Proteomic analysis identifies novel binding partners of BAP1 — R. Baas, F. J van der Wal, et al. (2021)

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