Abstract
The incidence of cutaneous malignant melanoma is increasing worldwide. While the treatment of initial stages of the disease is simple, the advanced disease frequently remains fatal despite novel therapeutic options . This requires identification of novel therapeutic targets in melanoma. Similarly to other types of tumours, the cancer microenvironment plays a prominent role and determines the biological properties of melanoma. Importantly, melanoma cell-produced exosomes represent an important tool of intercellular communication within this cancer ecosystem. We have focused on potential differences in the activity of exosomes produced by melanoma cells towards melanoma-associated fibroblasts and normal dermal fibroblasts. Cancer-associated fibroblasts were activated by the melanoma cell-produced exosomes significantly more than their normal counterparts, as assessed by increased transcription of genes for inflammation-supporting cytokines and chemokines, namely IL-6 or IL-8. We have observed that the response is dependent on the duration of the stimulus via exosomes and also on the quantity of exosomes. Our study demonstrates that melanoma-produced exosomes significantly stimulate the tumour-promoting proinflammatory activity of cancer-associated fibroblasts. This may represent a potential new target of oncologic therapy .
Highlights
Cancer incidence has reached a pandemic-like extent in numerous developed countries worldwide
We aimed to demonstrate in vitro the different effect of melanoma-produced exosomes on the functional properties of normal dermal fibroblasts and cancer-associated fibroblasts isolated from Cutaneous malignant melanoma (CMM)
The exosome production was studied in three malignant melanoma cell lines: A2058, BLM and G361
Summary
Cancer incidence has reached a pandemic-like extent in numerous developed countries worldwide. Histochemistry and Cell Biology contamination, through excessive caloric intake to civilisation-associated stressful lifestyle seem to contribute to this trend Another critical factor is ageing of the population (Smetana et al 2016). Among noncancerous cells forming the cancer ecosystem within the tumour niche, one has to emphasise the prominent role of different subtypes of immune cells and cancer-associated fibroblasts (CAFs) (Lacina et al 2015; Falcone et al 2020). These non-malignant cells can substantially influence the biological properties of cancer cells, resulting in their locally aggressive growth and increased migratory potential leading to metastatic spread (Kodet et al 2020). A distinct position in the regulation of the cancer ecosystem is held by IL-6 and IL-8 (Jobe et al 2016; Brábek et al 2020)
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