Low-dose photon irradiation induces invasiveness through the SDF-1α/CXCR4 pathway in malignant mesothelioma cells

Our plain-English summary of Low-dose photon irradiation induces invasiveness through the SDF-1α/CXCR4 pathway in malignant mesothelioma cells, by Y. Yamauchi, S. Safi, L. Orschiedt, et al (Oncotarget, 2017).

The study

• Authors: Y. Yamauchi, S. Safi, L. Orschiedt, A. Gardyan, S. Brons, J. Rieber, N.H. Nicolay, P.E. Huber, M. Eichhorn, H. Dienemann, F.J.F. Herth, K.J. Weber, J. Debus, H. Hoffmann, S. Rieken
• Journal: Oncotarget
• Published: 2017;8(40):68001-68011
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Low-dose photon irradiation has repeatedly been suspected to increase a risk of promoting local recurrence of disease or even systemic dissemination. The purpose of this study was to investigate the motility of malignant pleural mesothelioma (MPM) cell lines after low-doses of photon irradiation and to elucidate the mechanism of the detected phenotype.

Methods: H28 and H226 MPM cells were examined in clonogenic survival experiments and migration assays with and without various doses of photon and carbon ion irradiation. C-X-C chemokine receptor type 4 (CXCR4), SDF-1α, β1 integrin, α3 integrin, and α5 integrin expressions were analyzed by quantitative FACS analysis, ELISA and western blots. Apoptosis was assessed via Annexin-V-staining.

Results: The migration of MPM cells was stimulated by both fetal bovine serum and by stromal cell-derived factor 1α (SDF-1α). Low doses of photon irradiation (1 Gy and 2 Gy) suppressed clonogenicity, but promoted migration of both H28 and H226 cells through the SDF-1α/CXCR4 pathway. Hypermigration was inhibited by the administration of CXCR4 antagonist, AMD3100. In contrast, corresponding doses of carbon ion irradiation (0.3 Gy and 1 Gy) suppressed clonogenicity, but did not promote MPM cell migration.

Conclusion: Our findings suggest that the co-administration of photon irradiation and the CXCR4-antagonist AMD3100 or the use of carbon ions instead of photons may be possible solutions to reduce the risk of locoregional tumor recurrence after radiotherapy for MPM.

In plain English

This was a laboratory study of two lines of malignant pleural mesothelioma cells, H28 and H226, grown in the laboratory. No patients were studied, and the study did not examine asbestos exposure. The authors exposed the cells to single low doses of X-ray (photon) radiation (1 and 2 Gy) or carbon ion radiation (0.3 and 1 Gy), chosen to have similar biological effects. They then counted cells migrating through collagen-coated membranes. Photon radiation reduced colony formation but significantly increased migration in both cell lines. It also raised levels of a cell-surface receptor called CXCR4, without changing the integrins tested. The CXCR4-blocking drug AMD3100 almost fully reversed this extra migration. Carbon ions also reduced colony formation but caused only a minor, non-significant increase in migration and did not raise CXCR4. The authors concluded that adding AMD3100 to photon radiation, or using carbon ions instead, may be possible ways to reduce tumor recurrence after radiotherapy for mesothelioma. They noted the work was done only in cells, which may not reflect the situation in the body.

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: in vitro laboratory study of cultured mesothelioma cell lines (migration assays, clonogenic survival assays, FACS, ELISA, western blots, apoptosis assay)
• Who was studied: Two human malignant pleural mesothelioma cell lines, H28 and H226, purchased from ATCC; experiments by authors at Heidelberg, Germany; no patients or animals
• Exposure: Single doses of photon (X-ray) irradiation of 1 and 2 Gy, compared with carbon ion irradiation of 0.3 and 1 Gy, chosen to have the same biological effect; some cells were also treated with the CXCR4 antagonist AMD3100 (25 μg/ml). Asbestos was not an exposure in this study.
• Main results:
  • Compared with non-irradiated cells, photon irradiation significantly increased migration of H28 cells through collagen I-coated filters after 1 Gy and 2 Gy (p=0.009 and p=0.003) and through collagen IV-coated filters after 2 Gy (p<0.001). In H226 cells, 1 Gy and 2 Gy increased migration through both collagen I and IV-coated filters (p<0.001 and p=0.003).
  • Photon irradiation did not significantly change α3, α5 or β1 integrin expression in either cell line.
  • CXCR4 expression increased significantly on H28 cells after 2 Gy photons (p=0.005) and on H226 cells after 1 Gy and 2 Gy photons (p<0.001 and p=0.033).
  • Pre-treatment with the CXCR4 antagonist AMD3100 almost fully reversed photon-induced migration in both cell lines after 2 Gy, but did not affect migration of non-irradiated cells.
  • Carbon ion irradiation at 0.3 and 1 Gy produced only a minor, non-significant increase in migration in both cell lines.
  • Carbon ion irradiation did not stimulate CXCR4 expression on the surface of either cell line.
  • Both photon and carbon ion irradiation significantly reduced clonogenic survival, with no significant difference between corresponding doses. The authors reported no significant difference in apoptosis (data not shown).
• The authors' conclusion: The authors concluded that low-dose photon irradiation promoted mesothelioma cell migration through increased CXCR4 expression. They suggested that giving AMD3100 together with photon irradiation, or replacing photons with carbon ions, may be two possible solutions to improve radiation treatment in mesothelioma patients.
• Limitations the authors state:
  • The study was done only in cells in the laboratory, which may not reflect the situation in the body.
  • Effects of radiation on the tissue surrounding the tumor were not addressed.
  • Other pathways besides SDF-1α/CXCR4 may contribute to cell migration; only this pathway and integrins were examined, and no comprehensive analyses were performed.

Topics

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

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