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Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A

Ella Brandt1, Mutlu Keskin2, Ismo T Räisänen1

  • 1Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland.

Biomedicines
|January 26, 2024
PubMed

Insights

Radiotherapy for head and neck cancer (HNC) significantly alters biomarkers, increasing periodontal tissue destruction risk. An active matrix metalloproteinase-8 (aMMP-8) mouth-rinse test may detect this risk early in HNC patients undergoing RT.

Area of Science:

  • Biochemistry
  • Oncology
  • Periodontology

Background:

  • Head and neck cancer (HNC) radiotherapy (RT) effects on biomarkers are largely unknown.
  • Understanding these effects can lead to more precise cancer treatments and fewer side effects.
  • Biomarkers in mouth-rinse samples offer a non-invasive assessment method.

Purpose of the Study:

  • To investigate changes in matrix metalloproteinase (MMP)-8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO), and interleukin (IL)-6 levels during and after RT in HNC patients.
  • To assess the clinical periodontal status before and after RT.
  • To explore the potential of active MMP-8 (aMMP-8) as an early detection tool for RT-induced periodontal damage.

Main Methods:

  • A cohort study of 21 HNC patients receiving RT.
  • Periodontal examinations performed pre-RT and one month post-RT.
  • Mouth-rinse samples collected at three time points (pre-RT, mid-RT, post-RT) analyzed for biomarkers using point-of-care kits and ELISA.
  • Molecular forms of MMP-8 and MMP-9 analyzed by western immunoblot and zymography.

Main Results:

  • Significant increases observed in active and total MMP-8, active MMP-9, and IL-6 levels during RT, with subsequent decreases post-RT.
  • Elevated aMMP-8 levels persisted one month after RT compared to pre-RT levels.
  • Clinical periodontal parameters, including attachment loss and probing depths, worsened post-RT.
  • RT induced an active matrix metalloproteinase cascade, particularly prolonged aMMP-8 activity, suggesting increased periodontal tissue destruction risk.

Conclusions:

  • Radiotherapy for HNC elevates inflammatory biomarkers and increases the risk of periodontal tissue destruction.
  • Prolonged activity of collagenolytic aMMP-8 is a key factor in RT-induced periodontal damage.
  • The aMMP-8 point-of-care mouth-rinse test shows promise as an early detection tool for identifying HNC patients at risk of periodontal damage during RT.
Keywords:
aMMP-8biomarkerhead and neck cancermatrix metalloproteinaseperiodontitisradiotherapy

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