The role of growth factors and cytokines in the tumorigenesis and immunobiology of malignant mesothelioma

Our plain-English summary of The role of growth factors and cytokines in the tumorigenesis and immunobiology of malignant mesothelioma, by D.R. Fitzpatrick, D.J. Peroni, H. Bielefeldt-Ohmann (American Journal of Respiratory Cell and Molecular Biology, 1995).

The study

• Authors: D.R. Fitzpatrick, D.J. Peroni, H. Bielefeldt-Ohmann
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1995;12(5):455-60
• Type of article: Review
• Cited by: 68 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an asbestos-associated cancer that is increasing in incidence worldwide and is refractory to conventional therapy. MM cells are potent sources of a number of cytokines, some of which have recently been shown to be directly involved in the aggressive growth and spread of MM tumors. Emerging data also suggest involvement of MM-derived cytokines in systemic paraneoplastic syndromes including immunosuppression, thrombocytosis, cachexia, amyloidosis, and hypoglycemia. Additional characterization of the expression of cytokines and cytokine receptors in situ in MM tumors may provide a more complete picture of the autocrine and paracrine processes which occur in MM. Improved therapy of MM, particularly cytokine-based approaches, is likely to benefit from further elucidation of the patterns and regulation of cytokine expression associated with MM tumors.

In plain English

This 1995 article was a minireview, not a new study. The authors summarized published laboratory and clinical research on growth factors and cytokines (signalling proteins) made by malignant mesothelioma cells. It called mesothelioma asbestos-associated but did not examine asbestos exposure or fiber types. Reviewed studies reported that human and mouse mesothelioma cell lines made high levels of platelet-derived growth factor (PDGF), while two rat cell lines did not. Making a transformed human mesothelial cell line overproduce PDGF-A made it highly tumor-forming in mice. In a cited study by this article's authors and colleagues, lowering TGF-beta in mouse mesothelioma cells reduced their growth in soft agar and slowed tumor development in mice. In another mouse study, antibodies against interleukin-6 delayed wasting (cachexia) and death without significantly inhibiting tumor development. The authors argued that the cancer cells themselves were the most potent sources of many of these cytokines within tumors, though other nearby cells may modify their effects. They wrote that the findings suggest controlled modulation of these cytokines will be useful in therapy, perhaps especially for palliative treatment of advanced disease. They noted considerable cytokine variation between tumors.

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: Review (minireview) of published research; no new data were collected
• Who was studied: Not a population study. The review covered published studies of malignant mesothelioma cells and tumors, including human, mouse and rat cell lines, mouse tumor models, and samples from patients.
• Exposure: No asbestos exposure was studied. Asbestos is mentioned only as the cause of the cancer, and no fiber types are named. The review dealt with growth factors and cytokines made by mesothelioma cells (PDGF, TGF-beta, interleukin-6, colony-stimulating factors, IGF-I, IL-1 beta, bFGF) and with their receptors.
• Main results:
  • Reviewed studies: human and mouse mesothelioma cell lines expressed high levels of PDGF A and B, but two rat mesothelioma cell lines did not appear to express PDGF-A or -B at significant detectable levels.
  • Reviewed study (van der Meeren and colleagues): engineering a transformed human mesothelial cell line to overexpress PDGF-A made it highly tumor-forming in nude mice.
  • Reviewed study (reference 14, whose authors include this article's authors): in mouse mesothelioma cells, reducing TGF-beta expression was associated with specific inhibition of growth in soft agar.
  • The same study found retarded tumor development in a mouse model.
  • Reviewed study (Maeda and colleagues): TGF-beta2 levels in pleural effusions from mesothelioma patients were significantly higher than in pleural effusions from tuberculosis or other lung cancers.
  • Reviewed mouse study: neutralizing anti-IL-6 antibodies delayed cachexia, liver pathology and mortality without significantly inhibiting tumor development.
  • Reviewed reports: in patients with IL-6-producing mesothelioma tumors, systemic thrombocytosis or systemic amyloidosis was observed.
  • The authors' interpretation of the evidence: the mesothelioma cells themselves are the most potent sources of many (not all) cytokines within the tumors.
  • The authors also wrote that other cells within or near the tumors may augment, modify or amplify the cytokine-driven processes started by the mesothelioma cells.
• The authors' conclusion: The authors wrote that the recent findings suggest controlled modulation of mesothelioma-derived cytokines will be useful in therapy, perhaps especially for palliative treatment of advanced stages. This is a suggestion about future treatment, not a demonstrated benefit in patients.
• Limitations the authors state:
  • Cytokines vary considerably between mesothelioma cells and tumors, and not all of the pathways described may be active in all tumors.
  • Benign mesothelioma is extremely rare, and the authors knew of no cytokine studies on it.
  • Because of space limits, the literature was not comprehensively referenced.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytokine, Carcinogenesis, Mesothelioma, Cachexia.

Related studies

• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)
• Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture — E. Bermudez, J. Everitt, et al. (1990)
• The pathobiology of asbestos-induced lung disease: a proposed role for macrophage-derived growth factors — J.A. Lasky, J.C. Bonner, et al. (1991)
• Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages — P.W. Noble, F.R. Lake, et al. (1993)
• Serum oncoproteins and growth factors in asbestosis and silicosis patients — P.W. Brandt-Rauf, S. Smith, et al. (1992)
• Analyzing the genes and peptide growth factors expressed in lung cells in vivo consequent to asbestos exposure and in vitro — A.R. Brody, J.Y. Liu, et al. (1997)

Browse more research in American Journal of Respiratory Cell and Molecular Biology, or return to medical research.