Novel expression of kallikreins, kallikrein-related peptidases and kinin receptors in human pleural mesothelioma

Our plain-English summary of Novel expression of kallikreins, kallikrein-related peptidases and kinin receptors in human pleural mesothelioma, by J. Chee, J. Singh, A. Naran, et al (Biological Chemistry, 2007).

The study

• Authors: J. Chee, J. Singh, A. Naran, N.L. Misso, P.J. Thompson, K.D. Bhoola
• Journal: Biological Chemistry
• Published: 2007;388(11):1235-42
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is an aggressive cancer of the pleura that is causally related to exposure to asbestos fibres. The kallikrein serine proteases [tissue (hK1) and plasma (hKB1) kallikreins, and kallikrein-related peptidases (KRP/hK2-15)] and the mitogenic kinin peptides may have a role in tumourigenesis. However, it is not known whether hK1, hKB1, KRP/hK proteins or kinin receptors are expressed in pleural mesotheliomas. The expression of hK1, hKB1, KRP/hK2, 5, 6, 7, 8 and 9, and kinin B(1) and B(2) receptors was assessed in archived selected normal tissue and mesothelioma tumour sections by immunoperoxidase and immunofluorescence labelling. hK1, hKB1 and kinin B(1) and B(2) receptors were expressed in malignant cells of the epithelioid and sarcomatoid components of biphasic mesothelioma tumour cells. The percentage of cells with cytoplasmic and nuclear labelling and the intensity of labelling were similar for hK1, hKB1 and the kinin receptors. KRP/hK2, 6, 8 and 9 were also expressed in the cytoplasm and nuclei of mesothelioma cells, whereas KRP/hK5 and hK7 showed predominantly cytoplasmic localisation. This is a first report, but further studies are required to determine whether these proteins have a functional role in the pathogenesis of mesothelioma and/or may be potential biomarkers for pleural mesothelioma.

In plain English

This laboratory study looked at whether certain enzymes (tissue kallikrein, plasma kallikrein and six kallikrein-related peptidases: hK2, 5, 6, 7, 8 and 9) and two kinin receptors (B1 and B2) are present in pleural mesothelioma tumour tissue. The authors stained archived tumour specimens from four patients with biphasic mesothelioma, obtained from PathWest in Perth, Australia, and used normal lung, skin, brain and prostate tissue as comparison. Two observers judged what share of tumour cells stained and how strongly. In all four patients, tissue kallikrein stained the cytoplasm of 90% of tumour cells, more strongly than in control tissue. Plasma kallikrein and both receptors were also found in tumour cells, in varying proportions. The kallikrein-related peptidases were examined in tissue from one patient. All six stained the cell body, but hK5 did not stain cell nuclei. The study did not examine or report the patients' asbestos exposure. The authors concluded this was a first report and that further studies are needed to learn whether these proteins play a role in mesothelioma or could serve as biomarkers.

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 study of archived tumour tissue: proteins were detected with antibody staining (immunoperoxidase and immunofluorescence) and graded qualitatively under the microscope.
• Who was studied: Archived pleural mesothelioma tissue (biphasic subtype, with epithelioid and sarcomatoid cells) from four patients, obtained from the Department of Tissue Pathology, PathWest, Perth, Australia. The kallikrein-related peptidases were assessed in tissue from one of these patients. Normal lung, skin, brain and prostate tissue served as controls. Dates were not given.
• Exposure: Asbestos exposure was not studied. The article does not report the patients' asbestos exposure. What was measured was the presence of kallikreins, kallikrein-related peptidases and kinin receptors in tumour cells.
• Main results:
  • Tissue prokallikrein (hK1) stained the cytoplasm of 90% of malignant cells in both the epithelioid and sarcomatoid parts of the tumours, at an intensity greater than in control tissue. Nuclei of 50–60% of malignant cells stained at an intensity equivalent to control tissue.
  • The grading scale compared staining with control tissue: grade 1 meant less staining, grade 2 equivalent staining, and grade 3 greater staining than in the control tissue.
  • Plasma prekallikrein (hKB1) showed variable, low-intensity cytoplasmic staining (less than control) in 10–80% of tumour cells. Nuclear staining was seen in 60–80% of tumour cells.
  • Kinin B1 receptor: the text reports cytoplasmic labelling in 70–90% of malignant cells in both subtypes and nuclear staining in 50–70% of tumour cells.
  • Kinin B2 receptor: cytoplasmic staining was seen in 90–100% of malignant cells in three tissue sections and in 40–50% in one section. Nuclear labelling ranged from 40% to 60% of tumour cells.
  • The kallikrein-related peptidases were assessed in tumour tissue from one patient.
  • In that one patient, hK5 stained the cytoplasm of more than 80% of malignant cells, and nuclei were not labelled.
  • In that one patient, hK7 stained the cytoplasm of more than 80% of malignant cells, and about 5% of nuclei were labelled.
  • In that one patient, hK6 stained 90% of epithelioid malignant cells, with 30% of nuclei stained.
  • In that one patient, hK8 stained the cytoplasm of more than 80% of epithelial malignant cells, with nuclear staining in 30%.
  • In that one patient, hK2 stained 60% of epithelioid malignant cells (graded 1, less than control, although the text calls it intense), with nuclei stained in 30% of tumour cells.
  • In that one patient, hK9 showed granular cytoplasmic staining in more than 80% of malignant cells, with nuclear staining in 20%.
• The authors' conclusion: The authors concluded that this was the first study to show these kallikreins, kinin receptors and selected kallikrein-related peptidases are expressed in malignant mesotheliomas. They said further studies are required to determine whether the proteins have a functional role in mesothelioma or may be potential biomarkers for pleural mesothelioma.
• Limitations the authors state:
  • The authors note there are no data on what the presence of these proteins actually does in mesothelioma cells.
  • In normal lung control tissue, alveolar lining cells were not subtyped.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Pleura, Epithelioid, Sarcomatoid, Biphasic Mesothelioma, Biomarker.

Related studies

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• Expression and activity of urokinase and its receptor in endothelial and pulmonary epithelial cells exposed to asbestos — A. Barchowsky, R.R. Roussel, et al. (1998)
• Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture — E. Bermudez, J. Everitt, et al. (1990)
• Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells — R.C. Perkins, V.C. Broaddus, et al. (1999)
• Urokinase receptor in human malignant mesothelioma cells: role in tumor cell mitogenesis and proteolysis — S. Shetty, A. Kumar, et al. (1995)
• Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor — W.N. Rom (1991)

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