Melanoma is highly aggressive skin cancer, resistant to chemo- and radiotherapies at late stages. Many studies showed that this aggressiveness is connected with high heterogeneity of melanoma cells and is reflected in the presence of subpopulations displaying cancer stem cells (CSC) properties. While most of therapies aim at rapidly proliferating cells, CSC contribute to therapy resistance due to their slow proliferation rate. Although many antigens and functional features have been described as markers of melanoma initiating cells (MIC), there is still growing body of evidence showing that melanoma may not follow the canonical CSC hierarchy. Having this in mind there is still a need for studies under the biology of MIC cells.

 

One of the feature that contribute to melanoma invasiveness is the activity of heme oxygenase-1 (HO-1). HO-1 is heme degrading enzyme inducible in stress e.g. chemotherapy. In murine melanoma, HO-1 overexpression increases the invasiveness of cancer cells and vasculature of tumors. Moreover, people with higher HO-1 activity are more prone to develop melanoma. This data suggests an important role of HO-1 in melanoma biology, but there are no studies under the role of this enzyme in MIC subpopulations. The main aim of this project was to characterize the function of HO-1 in MIC subpopulations. What is more, we wanted to check the function of      HO-1 in pigmentation of melanoma and melanocytes.

 

Our data show that murine melanoma cell line B16-F10 contains highly heterogenous MIC subpopulations, including slowly cycling cells. B16-F10 cells robustly form clones from single cells in vitro and have abilities to initiate tumor growth (from as little as 10 cells) in vivo. Overexpression of HO-1 affects these abilities more than MIC markers expression. We found out that activity of HO-1 is necessary for non-adherent growth and for melanospheres formation in Matrigel - features attributed to CSC. Moreover, HO-1 seems to play important role in melanogenesis, especially in pathogenic conditions.

 

Overall our data help to understand the heterogeneity of melanoma, the phenomenon that is still one of the biggest challenge in the therapy of this cancer. Additionally, we discovered that activity of HO-1 play an important role in clonogenic potential and melanogenesis of melanoma cells.

 

Within the frame of this project Anna Kusienicka will visit the Department of Dermatology at Medical University of Vienna. She will have a chance to gain experience in the cutting-edge techniques (e.g. CROP-seq, scWGBS, ATAC-seq, sc-RNAseq) and work with melanoma patients material.