Anti-proliferative effect of histamine on squamous cell carcinoma of the skin and downregulation of vascular endothelial growth factor receptor-2

Introduction:

Squamous cell carcinoma of the skin is characterized as a malignant tumor that grows locally and destructively but rarely metastasizes, occurring 90% of the cases in the head and facial region. An intensive accumulation of mast cells around tumor tissue of squamous cell carcinoma of the skin is typically observed. However, their effects on squamous cell carcinoma remain largely unknown. The aim of the study was therefore to investigate effects of histamine on squamous cell carcinoma.

Methods:

Effects of the major mediator of mast cells, histamine, were investigated in an organotypic culture with two cell lines, SCC12 and SCC13. After 7 days of culture with histamine added 3 times (final concentration of 10^–5 M), an immunohistochemical study was performed using antibodies to bromodeoxyuridine (BrdU, incorporation for 48h), Ki-67, and vascular endothelial growth factor receptor-2 (VEGFR-2).

Results:

After incubation with histamine, the number of Ki-67-positive SCC12 and SCC13 cells was significantly reduced (by 54% and 25%, respectively). There was also a significant decrease in BrdU incorporation (by 29% and 60%, respectively). In addition, histamine led to a significant downregulation of VEGFR-2 in the two cell lines.

Conclusions:

This study suggested an anti-proliferative effect of histamine on squamous cell carcinoma of the skin by downregulating VEGFR-2 as a potential signaling pathway. Therefore, in further experiments, the behavior of squamous cell carcinoma on histamine in contrast to healthy keratinocytes should be characterized more accurately. Furthermore, a therapeutic possibility via VEGF signaling pathway should be tested.

Publication History

Publication Date:
18 April 2018 (online)