Expression of Antimicrobial Peptides by Uveal and Cutaneous Melanoma Cells and Investigation of Their Role in Tumor Cell Migration and Vasculogenic Mimicry

Abstract

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.

N-myc downstream–regulated gene 1 can promote vasculogenic mimicry and angiogenesis in urothelial carcinoma

“…Although this pattern appears as PAS +ve thin lines by light microscopy, Frenkel et al described that these structures appeared as hollow channels with blood circulation in their lumens by laser scanning confocal angiography in a choroidal melanoma [ 31 ]. Moreover, Manarang JC et al described that highly aggressive melanoma cells cultured in 3 dimensional matrix gel induced the formation of VM with characteristic looping patterns that can transmit fluids, while less aggressive cells did not produce these VM patterns when grown on similar conditions [ 32 ]. Interestingly, it has been also suggested that VM not only promotes tumor growth but also facilitate lymphovascular invasion.…”

LL-37 Might Promote Local Invasion of Melanoma by Activating Melanoma Cells and Tumor-Associated Macrophages

“…The expression of LL-37 on myeloid cells in dermis is correlated with levels of proinflammatory cytokines such as IL-23p19, IL-17A, and TNF-α [ 6 , 7 ], which could promote tumor progression via angiogenesis in melanoma and non-melanoma skin cancers [ 8 , 9 , 10 , 11 ]. Moreover, LL-37 is expressed in melanoma cells, potentially promoting their own proliferation, migration and invasion by autocrine and/or paracrine fashions [ 11 , 12 , 13 ]. Notably, dermal expression of LL-37 is increased in parallel with dermal invasion of tumor cells in skin cancers [ 14 , 15 ].…”