Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas

Our plain-English summary of Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas, by L.A. Goodglick, C.A. Vaslet, N.J. Messier, et al (Toxicologic Pathology, 1997).

The study

• Authors: L.A. Goodglick, C.A. Vaslet, N.J. Messier, A.B. Kane
• Journal: Toxicologic Pathology
• Published: 1997;25(6):565-73
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Repeated intraperitoneal injections of crocidolite asbestos fibers induced diffuse malignant mesotheliomas in mice. A series of mesothelial cell lines was isolated from mice at different stages in the development of these tumors. The cell lines isolated from mice with mesotheliomas recapitulated their growth pattern in vivo and were tumorigenic when reinjected into syngeneic mice. Similar to human mesothelial cells, growth of the murine cell lines was stimulated by epidermal growth factor. Reactive mesothelial cells and mesotheliomas expressed the receptor for this growth factor. Crocidolite asbestos fibers have been reported to induce sustained expression of the c-fos and c-jun protooncogenes in rat pleural mesothelial cells in vitro (Heintz et al, Proc. Natl. Acad. Sci. USA 90: 3299-303, 1993). Human malignant mesotheliomas have been shown to express c-fos in situ (Ramael et al, Histol. Histopathol. 10: 639-643, 1995). Two of the cell lines derived from highly invasive murine mesotheliomas overexpressed c-fos and c-jun. This murine model recapitulates the histopathology, growth factor responses, and protooncogene expression of human malignant mesotheliomas.

In plain English

This was a laboratory study in mice, not people. The authors gave male C57Bl/6 mice weekly injections into the abdominal cavity of crocidolite asbestos prepared to UICC standards, using long-fiber, short-fiber or mixed preparations. Malignant mesotheliomas were found after 35 to 66 weekly injections. The earliest appeared after 35 injections of long fibers. The authors grew cell lines from the lining cells of mice at different stages. Lines taken after 1 week of injections were established from only 10% of mice, and one such line (D9) did not form tumors when injected into other mice. Lines from mice with mesotheliomas were established with a 100% success rate and formed tumors in mice of the same strain. Epidermal growth factor at 5 ng/ml increased growth 1.3 to 2.0-fold in all lines except line 19. Two lines, 7 and 40, overexpressed the c-fos and c-jun genes, and both produced invasive tumors. The authors concluded that this mouse model recapitulates features of human malignant mesothelioma. They noted that injecting fibers directly is an unnatural route of exposure.

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: Animal experiment: mice were injected with asbestos, and cell lines grown from them were studied in culture and re-injected into mice
• Who was studied: Male C57Bl/6 mice, 1 to 2 months old, from Charles River Laboratories; cell lines were grown from mice after 1 to 60 weeks of injections
• Exposure: Weekly intraperitoneal injections of UICC crocidolite asbestos, as mixed (native) fibers or as samples enriched in short or long fibers
• Main results:
  • Malignant mesotheliomas were identified in mice after 35 to 66 weekly injections of long, short or mixed crocidolite
  • The laboratory reported no spontaneous mesotheliomas in uninjected or saline-injected mice over the previous 10 years
  • From mice injected for 1 week, cell lines could be established from only 10% of mice. From mice with mesotheliomas, cell lines were established with a 100% success rate
  • The nontumorigenic line D9 did not form tumors when re-injected, while lines from mice with mesotheliomas were tumorigenic
  • Lines from mice with early, focal mesotheliomas took 113 to 173 days to form tumors after re-injection. Lines from mice with diffuse peritoneal mesotheliomas formed tumors after subcutaneous injection in 7 to 80 days
  • Epidermal growth factor at 5 ng/ml stimulated growth 1.3 to 2.0-fold in all cell lines except line 19, which was the only line stimulated by PDGF
  • Reactive mesothelial cells and the mouse mesotheliomas showed staining for the epidermal growth factor receptor, especially in the epithelioid part of the tumors
  • Only two cell lines (7 and 40) overexpressed c-fos and c-jun relative to the reference gene GAPDH, and both were invasive when re-injected under the skin
  • All but one of the tested mesothelial cell lines (the exception was line 19) expressed varying levels of WT1 gene messages
• The authors' conclusion: The authors concluded that this mouse model recapitulates the histopathology, growth factor responses and protooncogene expression of human malignant mesotheliomas
• Limitations the authors state:
  • Injecting fibers directly into the pleural or peritoneal space is an unnatural route of exposure
  • The authors stated that further experiments in genetically engineered mice are needed to explore the role of c-fos

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Mesothelioma, Crocidolite, Malignant Mesothelioma, Reactive Mesothelial Cells, Histopathology.

Related studies

• Persistent induction of c-fos and c-jun expression by asbestos — N.H. Heintz, Y.M. Janssen, et al. (1993)
• Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers — Y.M. Janssen, N.H. Heintz, et al. (1994)
• Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture — E. Bermudez, J. Everitt, et al. (1990)
• 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)
• Monocyte-derived growth factors in asbestos-induced interstitial fibrosis — D.A. Schwartz, L. Rosenstock, et al. (1989)
• Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors — I.Y. Adamson, J. Bakowska, et al. (2000)

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