Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters

Pathol Oncol Res. 2017 Apr;23(2):345-353. doi: 10.1007/s12253-016-0102-5. Epub 2016 Sep 14.

Abstract

ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage. Twenty-five patients with OSCC and 25 healthy controls were included. Biopsies of tumor tissue from patients with OSCC and buccal mucosa in controls were obtained. ADAM10, Fas, and FasL were analyzed by Western blotting. sFasL was quantified by ELISA. ADAM10 and Fas decreased significantly in OSCC compared with controls. Relatedly, within the OSCC group, Fas and ADAM10 decreased in accordance with tumor disease stage; in stages I/II, as well as in tumors of smaller diameter (T1-T2), ADAM10 showed higher levels when compared to patients with T3-T4 tumors and in stage III-IV. FasL in the tumor microenvironment and serum FasL showed no significant differences between both groups. Levels of complete FasL and cleaved FasL were positively correlated in controls; this correlation is preserved in patients with tumors in early stages (I-II), but is lost in later stage (III-IV). The dysregulation of ADAM10, Fas and FasL could be useful indicators of the progression and severity of OSCC.

Keywords: ADAM10; Fas; FasL; Oral cancer; sFasL.

MeSH terms

  • ADAM10 Protein / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid Precursor Protein Secretases / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Fas Ligand Protein / metabolism*
  • Female
  • Humans
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Mouth Mucosa / metabolism
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology*
  • fas Receptor / metabolism*

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Proteins
  • fas Receptor
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • ADAM10 protein, human