| Autor: |
Kainulainen, Kirsi, Takabe, Piia, Heikkinen, Sami, Aaltonen, Niina, Motte, Carol de la, Rauhala, Leena, Durst, Franziska C., Oikari, Sanna, Hukkanen, Taija, Rahunen, Eija, Ikonen, Ella, Hartikainen, Jaana M., Ketola, Kirsi, Pasonen-Seppänen, Sanna |
| Zdroj: |
Journal of Investigative Dermatology; 20220101, Issue: Preprints |
| Abstrakt: |
The tumor microenvironment with distinctive cell types and a complex extracellular matrix has a tremendous impact on cancer progression. In the present study we investigated the effects of proinflammatory (M1) and immunosuppressive (M2) macrophages on hyaluronan (HA) matrix formation and inflammatory response in melanoma cells. Proinflammatory factors secreted from M1 macrophages stimulated the formation of a thick pericellular HA matrix in melanoma cells due to upregulation of HA synthase 2 (HAS2). HAS2silencing reversed the effect of M1 conditioned medium (CM) on pericellular HA coat formation, and interestingly it also partly downregulated the M1 CM -induced upregulation of inflammation-related genes (IL1β, IL6), as did the inhibitors for TNFR and IKKγ. Gene set enrichment analysis revealed that genes related to inflammatory responses and TNFα signaling via NF-κB are enriched in the M1 CM -treated melanoma cells. Moreover, the expression of MMP9 and 3D cell invasion were induced in these cells, while M2 macrophages had no effect on HA synthesis, inflammatory response nor invasion. Our results indicate that the activation of TNFR–NF-κB signaling in M1 CM -treated cells leads to HAS2upregulation, which associates with a pro-tumor inflammatory and invasive phenotype of melanoma cells. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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