Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos

Our plain-English summary of Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos, by S.P. Lenz, F.H. Green, P.G. Murphy, et al (Cancer Letters, 1993).

The study

• Authors: S.P. Lenz, F.H. Green, P.G. Murphy, M. Lee, D.A. Hart
• Journal: Cancer Letters
• Published: 1993;68(2-3):119-27
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We have investigated the expression of plasminogen activators (PAs) and PA inhibitors (PAIs) by an asbestos-induced mesothelioma. Using zymographic, immunological and biochemical techniques it was demonstrated that cell lines derived from the tumor express high levels of PAI and low levels of a UK-like PA. Adherent and partially non-adherent variants of the mesothelioma expressed indistinguishable amounts of PAI and UK. Based on partial biochemical characterization, the PAI secreted by the mesothelioma cells was a set of PAIs which consisted of PAI-1 in addition to other species. These observations indicate that the difference in growth phenotype of the adherent and partially non-adherent lines was not due to detectable differences in PA and PAI expression.

In plain English

This was a laboratory study of cancer cells grown from a mesothelioma in a rat. Fisher 344 rats were injected in the abdomen with 50 mg of crocidolite asbestos. Cells were taken from one rat that had an intraperitoneal (abdominal) biphasic mesothelioma detectable nine months after the injection. The authors grew two variants of these cells: one that stuck tightly to the culture flask (adherent) and one that tended to form floating clusters (non-adherent). They asked whether the two variants differed in making plasminogen activators, a kind of protein-cutting enzyme, and the inhibitors of those enzymes. Both variants released a main activator of about 37 kDa that resembled urokinase. Both also showed inhibitor activity made up of at least three components, of about 42, 47 and 55 kDa, and one was related to human PAI-1. The inhibitor patterns looked the same in both variants. However, more activator-inhibitor complexes formed with fluid from the adherent cells. Adding two test chemicals (PMA or retinoic acid) caused no detectable change in the inhibitors. The authors concluded that the differences between the variants were not due to detectable differences in activator and inhibitor expression.

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What the study did and found

• Design: Laboratory (in vitro) study of cell lines derived from an asbestos-induced rat mesothelioma, examining whether plasminogen activator (PA) and PA inhibitor (PAI) expression relate to whether cells adhere to the culture surface
• Who was studied: Cell lines grown from tumor foci of one Fisher 344 rat with an intraperitoneal biphasic mesothelioma detected nine months after asbestos injection. The cells were separated into an adherent (ADH, spindle-shaped/sarcomatous) variant and a non-adherent (NAD, epithelial) variant.
• Exposure: Rats were given 50 mg crocidolite asbestos in 10 ml saline by intraperitoneal injection. The cultured cells were also treated with phorbol myristate acetate (PMA) or retinoic acid.
• Main results:
  • In both ADH and NAD cells, the major plasminogen activator (about 37 kDa) was urokinase-like.
  • A second minor activator band of about 45 kDa was seen only in fluid from the ADH cells; its identity was not known.
  • Fluid from both ADH and NAD cells showed a broad band of PA inhibitory activity between 42 and 55 kDa, containing at least three inhibitors (about 42, 47 and 55 kDa).
  • At least one of the inhibitors (the 47 kDa one bound to an anti-human PAI-1 antibody column) was immunologically related to human PAI-1.
  • Treating either cell line with PMA or retinoic acid produced no detectable change in the pattern or intensity of PAI expression.
  • Inhibitor patterns were the same in both variants by reverse zymography. When the fluid was mixed with urokinase, higher levels of activator-inhibitor complexes were detected with fluid from the ADH cells.
• The authors' conclusion: The authors concluded that the differences in adherence pattern and metastatic behavior between the ADH and NAD cell lines were not due to detectable differences in PA and PAI expression.
• Limitations the authors state:
  • The authors state that the identity of the minor activator bands was not known.
  • The authors state that the inhibitors other than the PAI-1-related one were not identified.

Topics

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

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

Related studies

• Increased production of plasminogen activator inhibitor in vitro by pleural leukocytes from rats intratracheally instilled with crocidolite asbestos — X.Y. Li, G.M. Brown, et al. (1991)
• Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids — J. Hamilton, J.D. Vassalli, et al. (1976)
• Increased alveolar plasminogen activator in early asbestosis — A. Cantin, C. Allard, et al. (1989)
• Induction of macrophage plasminogen activator by asbestos is independent of PKC activation — D. Lison, F. Raguzzi, et al. (1991)
• Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells — R.C. Perkins, V.C. Broaddus, et al. (1999)
• Post-transcriptional regulation of plasminogen activator inhibitor type-1 expression in human pleural mesothelial cells — S. Shetty, T. Velusamy, et al. (2010)

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