Aims:
Antimicrobial peptides (AMPs) have been implicated in the pathogenesis of several cancers, although there is also evidence suggesting potential for novel, AMP-based anti-tumour therapies. Discerning potential roles of AMPs in tumour pathogenesis may provide valuable insight on mechanisms of novel AMP-based anti-tumour therapy.
Methods:
mRNA expression of the AMPs α defensin (HNP-1); cathelicidin (LL-37); and β defensins (hBD-1, hBD-2, hBD-3, hBD-4) in human uveal and cutaneous melanoma cell lines, primary human uveal melanocytes, and primary human uveal melanoma cells was determined by RT-PCR. An in vitro scratch assay and custom Matlab analysis were used to determine AMP effects on melanoma cell migration. Lastly, the effect of specific AMPs on vasculogenic mimicry was determined by 3D culture and light and fluorescence microscopy.
Results:
Low to moderate, AMP transcript levels were detected and these varied across the cells tested. Overall, LL-37 expression was increased while hBD-4 was decreased in most melanoma cell lines, compared to primary cultured uveal melanocytes. There was no observable influence of HNP-1 and LL-37 on tumour cell migration. Additionally, aggressive cutaneous melanoma cells grown in 3D cultures exhibited vasculogenic mimicry, although AMP exposure did not alter this process.
Conclusions:
Collectively, our data show that although AMP mRNA expression is variable between uveal and cutaneous melanoma cells, these peptides have little influence on major characteristics that contribute to tumour aggressiveness and progression.