Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

Our plain-English summary of Tumorigenic properties of alternative osteopontin isoforms in mesothelioma, by S.V. Ivanov, A.V. Ivanova, C.M. Goparaju, et al (Biochemical and Biophysical Research Communications, 2009).

The study

• Authors: S.V. Ivanov, A.V. Ivanova, C.M. Goparaju, Y. Chen, A. Beck, H.I. Pass
• Journal: Biochemical and Biophysical Research Communications
• Published: 2009;382(3):514-8
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.

In plain English

This laboratory study looked at osteopontin (SPP1), a protein the authors had previously linked to asbestos-induced malignant mesothelioma. SPP1 comes in three forms, called isoforms A, B and C. The authors measured RNA for each isoform in mesothelioma tissue and unaffected peritoneum from 46 patients operated on at Wayne State University between 1998 and 2005. Isoforms A and B were higher in the tumor in 23 of 31 matched tumor and normal pairs, with isoform A reaching 137-fold in one patient. Isoform C was barely detectable in tumors. In one patient, a tumor after recurrence showed 9-fold and 16-fold increases in A and B compared with the earlier tumor. The authors then made two mesothelioma cell lines produce each isoform. Isoform A, but not B or C, increased cell growth (1.7-fold in H2595, 1.4-fold in HP-1) and promoted cell migration. Isoforms A and B stimulated invasion, and all three isoforms increased colony formation in H2595 cells. The authors concluded that isoforms A and B are highly induced in mesothelioma and may serve as diagnostic markers. The study did not examine asbestos exposure.

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: RNA measurement (RT-PCR) of SPP1 isoforms in patient tumor and normal tissue, plus experiments in two mesothelioma cell lines made to express each isoform
• Who was studied: Mesothelioma and unaffected peritoneum specimens from 46 patients who had mesothelioma resection at Wayne State University, Detroit, 1998 to 2005 (78 RNA samples, 62 of them tumor and normal matched); two mesothelioma cell lines, HP-1 (biphasic) and H2595 (epithelial)
• Exposure: No asbestos exposure was measured. The experimental factor was expression of SPP1 (osteopontin) isoforms A, B and C, introduced into cell lines with expression plasmids
• Main results:
  • Isoforms A and B were up-regulated in 23 of 31 matched tumor and normal peritoneum pairs
  • Isoform A up-regulation reached 137-fold in one patient (patient 347)
  • Isoform C was underrepresented in healthy peritoneum and barely detectable in tumors
  • In one patient, a tumor taken after recurrence showed 9-fold (SPP1-A) and 16-fold (SPP1-B) increases compared with the earlier tumor
  • SPP1-A, but not B or C, increased proliferation in H2595 cells (1.7-fold, p less than 0.001)
  • A similar pattern was seen in HP-1 cells (1.4-fold, p less than 0.003)
  • SPP1-A over-expression promoted cell migration 1.3- to 1.8-fold in the wound closure assay in the two cell lines
  • All three isoforms increased the ability of H2595 cells to form colonies in soft agar
  • Isoforms A and B stimulated invasion. Isoform C had no effect in H2595 cells and a moderate suppressive effect in HP-1 cells
• The authors' conclusion: The authors concluded that isoforms A and B, but not C, are highly induced in mesothelioma, may serve as diagnostic markers, and justify further research into their roles in tumor progression
• Limitations the authors state:
  • The soft agar colony result was obtained in only one cell line. It remains to be seen whether it can be reproduced in another mesothelioma cell line
  • The authors said a follow-up study at the protein level is needed. Such a study would require specific antibodies for the three isoforms
  • It is not clear how common the observed differences between isoforms are. The authors said the study should be extended to other cancers

Topics

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

Medical terms in this study, explained in our Lexicon: Osteopontin, Mesothelioma, Cytokine, Malignant Mesothelioma, Pleura.

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• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
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