HIF-1α, NOTCH1, ADAM12, and HB-EGF are overexpressed in mucoepidermoid carcinoma

Oral Surg Oral Med Oral Pathol Oral Radiol. 2019 Jan;127(1):e8-e17. doi: 10.1016/j.oooo.2018.09.013. Epub 2018 Oct 5.

Abstract

Objective: Intratumoral hypoxia (IH) occurs during cellular proliferation of malignant tumors. This phenomenon is characterized by a decrease in oxygen levels in the neoplastic microenvironment. Throughout this condition, the proteins HIF-1α, NOTCH1, ADAM12, and HB-EGF can be activated, triggering signaling pathways associated with tumor invasiveness through invadopodia formation. This study aimed to evaluate the immunostaining of HIF-1α, NOTCH1, ADAM12, and HBEGF in 19 cases of mucoepidermoid carcinoma (MEC) and 10 samples of salivary glands (control group).

Study design: The immunoperoxidase technique was employed to detect the proteins of interest. The Student t test was used to compare immunoexpression between MEC samples and the control group.

Results: Protein immunostaining was statistically significantly higher in MEC samples than in the control group (P < .01), and the proteins were especially overexpressed in epidermoid cells of MEC.

Conclusions: We suggest that there is an association between the NOTCH1 signaling pathway activated by IH and the biologic behavior of MEC.

MeSH terms

  • ADAM12 Protein* / metabolism
  • Carcinoma, Mucoepidermoid* / metabolism
  • Cell Proliferation
  • Heparin-binding EGF-like Growth Factor* / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Neoplasm Invasiveness
  • Receptor, Notch1* / metabolism
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • HBEGF protein, human
  • HIF1A protein, human
  • Heparin-binding EGF-like Growth Factor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NOTCH1 protein, human
  • Receptor, Notch1
  • ADAM12 Protein
  • ADAM12 protein, human