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

Yoshikane Yamauchi1, Seyer Safi1, Lena Orschiedt2,3

  • 1Department of Thoracic Surgery, Thorax Clinic, Heidelberg University, Heidelberg, Germany.

Oncotarget
|October 6, 2017
PubMed
Abstract

Insights

Low-dose photon radiation increases malignant pleural mesothelioma cell migration via the SDF-1α/CXCR4 pathway. Carbon ions did not promote migration, suggesting alternative radiotherapy strategies to reduce recurrence risk.

Area of Science:

  • Oncology
  • Radiotherapy
  • Cell Biology

Background:

  • Low-dose photon irradiation is suspected to increase local recurrence and systemic dissemination risks.
  • Malignant pleural mesothelioma (MPM) is a challenging cancer with limited treatment options.

Purpose of the Study:

  • To investigate the effect of low-dose photon irradiation on MPM cell motility.
  • To elucidate the underlying molecular mechanisms of radiation-induced changes in MPM cell behavior.

Main Methods:

  • Clonogenic survival and migration assays were performed on MPM cell lines (H28, H226).
  • Cells were exposed to photon and carbon ion irradiation at various doses.
  • Expression of CXCR4, SDF-1α, and integrins was analyzed using FACS, ELISA, and Western blot.
  • Apoptosis was assessed via Annexin-V staining.

Main Results:

  • Low-dose photon irradiation (1-2 Gy) suppressed clonogenicity but promoted MPM cell migration.
  • MPM cell migration was enhanced via the stromal cell-derived factor 1α (SDF-1α)/C-X-C chemokine receptor type 4 (CXCR4) pathway.
  • The CXCR4 antagonist AMD3100 inhibited photon irradiation-induced hypermigration.
  • Carbon ion irradiation (0.3-1 Gy) suppressed clonogenicity without promoting migration.

Conclusions:

  • Photon irradiation at low doses can enhance MPM cell migration through the SDF-1α/CXCR4 pathway.
  • Carbon ion irradiation may offer a safer alternative by not promoting cell migration.
  • Co-administration of photon irradiation with CXCR4 antagonists or using carbon ions could reduce locoregional recurrence risk in MPM radiotherapy.