Lung tumor cells: a multivariate approach to cell classification using two-dimensional protein pattern

Our plain-English summary of Lung tumor cells: a multivariate approach to cell classification using two-dimensional protein pattern, by H.R. Schmid, D. Schmitter, P. Blum, et al (Electrophoresis, 1995).

The study

• Authors: H.R. Schmid, D. Schmitter, P. Blum, M. Miller, D. Vonderschmitt
• Journal: Electrophoresis
• Published: 1995;16(10):1961-8
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful research tool for the analytical separation of cellular proteins. The qualitative and quantitative pattern of polypeptides synthesized by a cell represents its phenotype and thus defines characteristics such as the morphology and the biological behavior of the cell. By analyzing and comparing the protein patterns of different cells it is possible to recognize the cell type and also to identify the most typical features of these cells. In applied pathology it is often difficult to identify the tissue of origin and the stage or grade of a neoplasia by cellular morphology analyzed by classical or immunostaining procedures. The protein pattern itself is the most characteristic feature of a cell and should therefore contribute to the identification of the cell type. For this reason we separated protein fractions originating from different lung tumor cell lines using 2-D PAGE and we compared the resulting patterns on a multivariate statistical level using correspondence analysis (CA) and ascendant hierarchical clustering (AHC). The results indicate that (i) protein patterns are highly typical for cells and that (ii) the comparison of the protein patterns of a set of interesting cell types allows the identification of potentially new marker proteins. 2-D PAGE is thus a unique and powerful tool for molecular cytology or histopathology, unveiling the protein expression level of tissues or cells.

In plain English

This laboratory study did not involve people or asbestos exposure. The authors grew 14 lung tumor cell lines: five mesothelioma, five small cell lung cancer, two adenocarcinoma, one squamous cell carcinoma and one large cell carcinoma. They extracted cytoskeletal and membrane-associated proteins from each line and separated them by two-dimensional gel electrophoresis. They compared the resulting spot patterns using correspondence analysis and hierarchical clustering. Each gel showed about 400 protein spots, many shared across lines. The clustering formed two main groups. One held the five mesothelioma lines. The other held the remaining nine, within which the small cell lines and the adenocarcinoma lines formed separate clusters. The squamous and large cell lines, also in this group, stood apart; the authors said they did not seem to belong to any of the other groups. Three of the eight spots that best separated the lines were identified: vimentin, cytokeratin 18 and cytokeratin 19. The authors concluded that protein patterns are highly typical for cells and could help identify new marker proteins. They suggested the method could contribute "to a certain extent" to telling mesotheliomas from adenocarcinomas.

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 cultured tumor cell lines, comparing two-dimensional gel electrophoresis protein patterns with multivariate statistics (correspondence analysis and ascendant hierarchical clustering)
• Who was studied: 14 cultured lung tumor cell lines: 5 mesothelioma (ZL5, ZL34, ZL55, SPC111, SPC212), 5 small cell lung cancer (OH1, OH3, SW2, NCI-H249, NCI-N417), 2 adenocarcinoma (A427, Calu6), 1 squamous cell carcinoma (U1752) and 1 large cell carcinoma (SLC-6); work done at University Hospital Zurich
• Main results:
  • About 400 distinct protein spots were detected per gel, and the 14 cell lines shared a large number of protein spots
  • In a plot of the first two statistical factors, which carried 45% of the total information, the mesothelioma cell lines (1, 4, 9, 11, 13) formed a separate group on one side
  • Clustering produced two main groups: the five mesothelioma lines (ZL5, SPC212, ZL34, SPC111, ZL55), and nine other lines, subdivided into small cell lung cancer lines (OH1, SW2, OH3, H249, N417) and adenocarcinoma lines (A427, Calu6)
  • Within the nine-line group, the squamous cell line U1752 and the large cell lung cancer line SLC6 were distinctly separated and, in the authors' words, did not seem to belong to any of the other groups
  • Of the 8 most discriminating protein spots, shown on mesothelioma cell line SPC212, three were identified by immunoblotting: cytokeratin 19, cytokeratin 18 and vimentin; the others were not identified
• The authors' conclusion: The authors concluded that protein patterns are highly typical for cells and that comparing them can identify potentially new marker proteins. They suggested the method could contribute to some extent to distinguishing mesotheliomas from adenocarcinomas, which they described as still a problem at diagnosis.
• Limitations the authors state:
  • The identity of most of the characteristic proteins found was unknown
  • The authors described the classification approach as only a starting point for further investigations

Topics

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

Medical terms in this study, explained in our Lexicon: Pathology, Cytology, Histopathology.

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