The effect of selective tyrosine kinase inhibitors on the expression of CD44 and AREG in HPV-positive and -negative squamous cell carcinoma

Introduction:

As cell surface protein, CD44 influences cell proliferation and differentiation and thus influences tumor progression. Amphiregulin (AREG) belongs to the family of epidermal growth factors (EGF) and plays an important role in the activation of EGFR. The alteration of the expression of these two target proteins after treatment with the tyrosine kinase inhibitors gefitinib, erlotinib, afatinib, dasatinib and nilotinib in HPV-positive and HPV-negative tumor cell lines was investigated.

Methods:

The protein expression of CD44 and AREG was determined by sandwich ELISA in tumor cell lines HNSCC 11A, HNSCC 14C and CERV196. The tested drugs were added at a target concentration of 20 µmol/l and incubated for 24 – 96 hours and compared with a chemonaive negative control.

Results:

The expression of AREG in the HPV-negative cell lines was reduced by all of the tested drugs. Interestingly, the protein concentration of AREG in the HPV-positive tumor cells was significantly decreased. In addition, AREG expression increased after incubation with nilotinib in HPV-positive tumor cells. The expression of CD44 could be significantly influenced by all drugs. The expression under selective EGFR inhibition was mostly reduced, whereas nilotinib led to a paradoxical increase of CD44 expression.

Discussion:

The results of this study show promising potential target proteins and their response to selective drug treatment options for head and neck cancer. The combination with selective tyrosine kinase inhibitors could lead to a better outcome in the future and improve the prognosis of patients with head and neck cancer.

Publication History

Publication Date:
23 April 2019 (online)