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Targeted Treatment of HPV16-positive and -negative SCC Cells With Small Molecule Tyrosine Kinase Inhibitors and

Lena Huber1, Richard Birk2, Manuel Knuettel3

  • 1Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; lena.huber@umm.de.

Anticancer Research
|July 5, 2022
PubMed
Abstract

Insights

Targeted therapies, including tyrosine kinase inhibitors (TKIs) and mTOR inhibitors, effectively alter matrix metalloproteinase (MMP) expression in head and neck squamous cell carcinoma (HNSCC) cell lines. These findings suggest MMPs as potential therapeutic targets in HNSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Targeted therapies have expanded treatment options for head and neck squamous cell carcinoma (HNSCC).
  • Matrix metalloproteinases (MMPs) are crucial in cancer development and represent promising therapeutic targets.
  • Investigating MMP2 and MMP14 expression in response to targeted agents is essential for HNSCC treatment strategies.

Purpose of the Study:

  • To examine the expression patterns of MMP2 and MMP14 in human papillomavirus (HPV)-positive and -negative HNSCC cell lines.
  • To evaluate the effects of small molecule tyrosine kinase inhibitors (TKIs) and an mTOR inhibitor on MMP expression in vitro.

Main Methods:

  • Utilized two HPV-negative (UMSCC-11A/-14C) and one HPV-positive (CERV196) HNSCC cell lines.
  • Treated cells with erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 hours.
  • Assessed cell proliferation and quantified MMP2 and MMP14 protein concentrations using ELISA.

Main Results:

  • MMP2 and MMP14 were expressed in all tested cell lines, with highest levels in UMSCC-14C.
  • TKIs significantly reduced MMP2 expression in the UMSCC-14C cell line (p<0.05).
  • In the HPV-positive cell line, tested drugs increased MMP2 and MMP14 expression.

Conclusions:

  • MMP signaling dysregulation contributes to HNSCC tumorigenesis and metastasis; MMP2 may serve as a biomarker.
  • Small molecule TKIs and everolimus effectively influence MMP2 and MMP14 expression.
  • Further research is needed to elucidate the interplay between the tumor microenvironment and tumor cells in HNSCC.
Keywords:
MMP14MMP2dasatinibdrug resistanceerlotinibgefitinibhead and neck squamous cell carcinomanilotinib

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