Fibronectin expression and organization in mesothelial and mesothelioma cells

Our plain-English summary of Fibronectin expression and organization in mesothelial and mesothelioma cells, by P.C. Ferriola, W. Stewart (The American Journal of Physiology, 1996).

The study

• Authors: P.C. Ferriola, W. Stewart
• Journal: The American Journal of Physiology
• Published: 1996;271(5 Pt 1):L804-12
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelial cells are believed to be the progenitor cells for malignant mesothelioma, a tumor associated with exposure to asbestos and other mineral fibers. Little is known regarding fibronectin (Fn) function in mesothelial and mesothelioma cells. Fn RNA, protein levels, and localization were assessed in secondary cultures and later passages of spontaneously immortalized rat pleural mesothelial (NRM) cells and in neoplastic cell lines derived from asbestos-induced mesotheliomas. NRM cells expressed similar levels of Fn RNA regardless of passage number or cell density, as determined by Northern blotting and ribonuclease protection assays. Western blotting showed that Fn protein was both secreted by NRM cells and associated with cell lysates. Immunofluorescent confocal laser scanning microscopy demonstrated that secondary cultures of NRM cells assembled Fn into abundant homogeneous fibrillar arrays organized primarily between cells, whereas later passages of NRM cells displayed abundant but less homogeneous Fn organization. Fn RNA and protein levels in neoplastic mesothelial cells were slightly less or similar to levels in NRM cells. Organization of Fn in neoplastic cells was heterogeneous compared with secondary cultures of NRM cells, but Fn fibril formation was still apparent. F-actin microfilaments were organized in both NRM and neoplastic cells; however, actin stress fibers were maintained in neoplastic cells, whereas NRM cells displayed dense actin peripheral bands at high density. The maintenance of organized Fn and actin in mesothelioma cells is surprising and may contribute to the localized growth and invasive properties of these tumors.

In plain English

This laboratory study compared fibronectin, a fiber-forming protein, in non-cancerous rat pleural mesothelial cells and in cell lines from asbestos-induced mesotheliomas in Fischer 344 rats. Three tumor lines came from peritoneal mesotheliomas and two (TO8, T10) from pleural mesotheliomas. The methods do not say which asbestos fiber type induced these tumors. Fibronectin RNA was two to four times lower in the tumor lines than in non-cancerous cells, except in TO8 and T10, which were similar. In growing cells, the non-cancerous cells and T10 secreted more fibronectin than the other four tumor lines. The authors reported this difference as statistically different by t-test. Tumor cells still built fibronectin fibers, but less evenly. At high density, non-cancerous cells formed dense actin bands typical of stationary cells. Tumor cells instead extended actin into lamellipodia, which the authors described as migratory. The authors concluded this fibronectin may contribute to the tumors' localized growth and invasive properties. They noted that differences between lines might reflect the tumors' site of origin.

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) cell-culture study comparing non-tumorigenic rat mesothelial cells with rat mesothelioma cell lines
• Who was studied: Rat cells only, with no human subjects. Pleural mesothelial cells came from 10- to 14-week-old Fischer 344 rats, and spontaneously immortalized lines (NRM2, SFM1) were derived from them. Mesothelioma cell lines 1114, 1145 and 1112 came from peritoneal mesotheliomas in F344 rats, and lines TO8 and T10 came from pleural mesotheliomas.
• Exposure: The tumor cell lines came from mesotheliomas induced in rats by asbestos; the peritoneal tumors arose after instillation of asbestos. The methods do not state the fiber type used for these lines. A cited reference title mentions erionite and UICC chrysotile asbestos, but the article does not tie a fiber type to each studied line. No exposure was applied to cells in this study.
• Main results:
  • Fibronectin RNA levels were two to four times lower in the tumor-derived cell lines than in the NRM (non-tumorigenic) cells. The exceptions were the T10 and TO8 lines, which had levels similar to NRM cells.
  • All cell lines had similar fibronectin RNA levels regardless of growth stage, except TO8, which had greater levels at the plateau phase of growth.
  • Fibronectin RNA levels measured by RPA were similar in SFM1 cells, in secondary cultures of NRM cells, and in later passages (up to passage 100) of NRM2 cells.
  • No vitronectin RNA was detected in the NRM cells or the tumor cells.
  • A single fibronectin protein band of 220 kDa was found in both the culture media and the cell extracts of the non-tumor and tumor cell lines.
  • In logarithmically growing cells, NRM and T10 cells secreted more fibronectin than the 1114, 1145, 1112 and TO8 lines. The authors reported these higher levels as statistically different from the other cell lines by t-test. The amounts are not given here because the mass unit is unreadable in the scan.
  • Confluent secondary cultures of NRM cells formed an extensive, even, organized fibronectin fiber network between cells. In later-passage NRM cells the network was dense but less highly organized.
  • The TO8 and T10 tumor cells showed an uneven distribution of fibronectin fibers, but the fibers were abundant and long.
  • Lines 1145 and 1112 showed shorter fibronectin fibers. In 1145 cells the fibronectin lay mainly toward the base of the cells.
  • At higher density, NRM cells organized actin into dense peripheral bands, which the authors took to indicate stationary, non-migratory cells.
  • High-density mesothelioma cells did not form these bands. They instead extended actin filaments into lamellipodia, which the authors described as indicative of a migratory phenotype.
• The authors' conclusion: The authors concluded that the abundant cell-associated fibronectin in these cells may contribute to the localized growth and invasive properties of mesotheliomas. They added that it may provide potential markers for diagnosis and treatment.
• Limitations the authors state:
  • TO8 and T10 were the only lines of pleural origin; the other tumor lines came from peritoneal tumors. Because of this, the authors could not rule out that differences between the cell lines were due to the tumors' site of origin.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Mesothelial Cells, Malignant Mesothelioma, Mineral Fiber, Fibril.

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