Tenascin and fibronectin expression in human mesothelial cells and pleural mesothelioma cell-line cells

Our plain-English summary of Tenascin and fibronectin expression in human mesothelial cells and pleural mesothelioma cell-line cells, by V.L. Kinnula, A. Linnala, E. Viitala, et al (American Journal of Respiratory Cell and Molecular Biology, 1998).

The study

• Authors: V.L. Kinnula, A. Linnala, E. Viitala, K. Linnainmaa, I. Virtanen
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1998;19(3):445-52
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Fibronectin (Fn) and tenascin (Tn) are two major extracellular matrix (ECM) glycoproteins that may have important roles both in fibrotic lung diseases and in lung tumors. The significance of Fn and Tn in human pleural mesothelial cells and pleural diseases is unclear. Transformed human pleural mesothelial cells (Met5A), primary cultures of mesothelial cells, and cultured mesothelioma cell lines were investigated for Fn and Tn immunoreactivity. Mesothelial cells were exposed for 48 to 96 h to transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), amosite asbestos fibers, or oxidants (H2O2 and menadione, a compound that auto-oxidizes to produce superoxide). Immunofluorescence and Western blotting with monoclonal anti-Fn and anti-Tn antibodies, and Northern blotting with a complementary DNA (cDNA) probe for Tn showed that mesothelial cells are capable of producing Fn and Tn. The mRNA level and immunoreactivity of Tn was enhanced by TGF-beta and TNF-alpha, whereas Fn was intensified only by TGF-beta. A wide range of amosite, H2O2, or menadione concentrations had no clear effect on Fn or Tn reactivity. Fn and Tn were present at low or undetectable concentrations in five of six mesothelioma cell lines, whereas the organization of Fn immunoreactivity in these cell lines was variable. Furthermore, results obtained with the tumor tissue of these same mesothelioma patients suggested that Fn and Tn expressions do not necessarily parallel either each other or results obtained with the cultured cells.

In plain English

This laboratory study asked whether human pleural mesothelial cells make two tissue proteins, tenascin and fibronectin, and what changes how much they make. The authors exposed an immortalized human mesothelial cell line (Met5A) to TGF-beta and TNF-alpha (two inflammatory signalling proteins), amosite asbestos fibers, and two oxidants (hydrogen peroxide and menadione). Further experiments used primary cultures of nonmalignant human pleural mesothelial cells. The cells made low levels of both proteins. TGF-beta increased both, and TNF-alpha marginally increased tenascin. Amosite did not raise either protein. The two higher doses reduced the number of living cells and slightly lowered fibronectin, and a non-toxic dose given for 72 hours produced no change. In six cell lines grown from mesothelioma patients' tumors, the proteins were mostly low or undetectable. In autopsy tumor tissue from the same patients, staining was highly variable. The authors concluded that TGF-beta can modulate both proteins in these cells. They noted that their results do not rule out effects of chronic asbestos exposure, and that autopsy tissue is not ideal material for this question.

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 (in vitro) study of cultured human mesothelial and mesothelioma cells, with immunostaining of autopsy tumor tissue
• Who was studied: An immortalized human mesothelial cell line (Met5A); primary cultures of nonmalignant human pleural mesothelial cells; six mesothelioma cell lines (M9K, M10K, M14K, M28K, M33K, M38K) established from the tumors of six mesothelioma patients; and autopsy tumor tissue from the same six patients
• Exposure: Amosite asbestos fibers at three doses (printed as 1 to 10 mg/cm2), TGF-beta1 (1 ng/ml), TNF-alpha (10 ng/ml), hydrogen peroxide and menadione, alone or in combination with TGF-beta, for 24 to 96 hours
• Main results:
  • In Met5A cells, the two higher amosite doses reduced the number of viable cells by 18% and 75% after 48 hours
  • In Met5A cells, tenascin increased after 48 hours with TGF-beta and marginally with TNF-alpha, but not with the lowest oxidant concentrations; other oxidant concentrations and all three fiber concentrations also showed no tenascin induction
  • Tenascin messenger RNA (both transcripts) in Met5A cells was raised by TGF-beta and TNF-alpha, and very marginally by amosite
  • In Met5A cells, fibronectin was increased by TGF-beta but not by TNF-alpha or non-toxic oxidant concentrations; higher hydrogen peroxide concentrations caused slight increases
  • The two higher amosite doses slightly decreased fibronectin in Met5A cells, which the authors suggest may be due to fiber toxicity
  • A non-toxic amosite dose given to Met5A cells for 72 hours produced no change in fibronectin or tenascin
  • Primary-cultured mesothelial cells confirmed tenascin induction by TGF-beta, but not by non-toxic concentrations of asbestos fibers or hydrogen peroxide
  • In the mesothelioma cell lines (Western blotting), fibronectin was prominent only in M33K and tenascin was detected only in M9K; M10K and M28K had weak fibronectin and no tenascin
  • In autopsy tumor tissue from the six patients, tenascin and fibronectin staining was highly variable with no constant pattern; fibronectin was moderate or abundant in five of six cases
• The authors' conclusion: The authors concluded that human pleural mesothelial cells produce fibronectin and tenascin, that this production can be modulated in vitro by TGF-beta, and that expression in cultured cells did not necessarily parallel expression in autopsy material
• Limitations the authors state:
  • The authors state that their results do not exclude fibronectin or tenascin induction by chronic asbestos exposure
  • The authors state that the difference from earlier rat studies may reflect different species, the immortalized cell line used, a different fiber type, or fiber toxicity
  • The authors state that low levels of these proteins in cultured cells might not reflect the situation in the body
  • The authors state that autopsy material is not ideal for studying these proteins in malignant tumor

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Pleural Mesothelioma, Glycoprotein, Mesothelioma, Transforming Growth Factor-beta (TGF-β), Tumor Necrosis Factor-alpha (TNF-α), Amosite, Superoxide.

Related studies

• Tenascin expression and distribution in pleural inflammatory and fibrotic diseases — R. Kaarteenaho-Wiik, E. Lakari, et al. (2000)
• Fibronectin expression and organization in mesothelial and mesothelioma cells — P.C. Ferriola, W. Stewart (1996)
• Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1 — S. Han, J.D. Ritzenthaler, et al. (2005)
• Expression of cell adhesion molecules and connexins in gap junctional intercellular communication deficient human mesothelioma tumour cell lines and communication competent primary mesothelial cells — K. Pelin, A. Hirvonen, et al. (1994)
• Tenascin XB Is a Novel Diagnostic Marker for Malignant Mesothelioma — K. Nakayama, M. Seike, et al. (2019)
• Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers — M. Maeda, H. Matsuzaki, et al. (2018)

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