Gala of Polish Science 2025. Award for the research team of prof. Dorota Nowak from the UWr Faculty of Biotechnology
Prof. Dorota Nowak and her team have been recognized by the Minister of Science and Higher Education. The award for significant achievements in scientific activity was presented on February 19 during the Polish Science Gala 2025 in Toruń. Congratulations!
The authors of the achievement entitled Characterization of mutual interactions between melanoma and colorectal cancer cells and cells present in the microenvironment of these cancers are employees and doctoral students of the Faculty of Biotechnology of the University of Wrocław in cooperation with scientists from the Wroclaw Medical University.
– For me and my team, this award is a summary of our activities over the past years – says prof. Dorota Nowak. – The research team that I have managed to create is an example of ideal cooperation in the field of medical sciences, cooperation between advanced basic research conducted at the Faculty of Biotechnology and clinical trials conducted at the Wroclaw Medical University and the Lower Silesian Center of Oncology, Pulmonology and Hematology in Wrocław – emphasizes our researcher.
The core of the research team consists of: prof. Dorota Nowak, dr Aleksandra Simiczyjew and dr Katarzyna Pietraszek-Gremplewicz, who are the main authors of the research concepts and the experiments carried out.
The other co-authors of the publication are: prof. Rafał Matkowski (Wroclaw Medical University), dr Marcin Ziętek (Wroclaw Medical University), dr Justyna Wądzyńska, dr Ewelina Dratkiewicz, dr Michał Majkowski, mgr Joanna Olszańska, mgr Mikołaj Domagalski, mgr Magdalena Kot, mgr Dominika Wilk
Prof. Dorota Nowak’s team focused their research on the previously overlooked characteristics of cancer niche cells formed as a result of the incubation of normal fibroblasts, adipocytes and keratinocytes with melanoma cells. Previous work by other researchers has focused almost exclusively on determining the effect of melanoma microenvironment cells on cancer cells. Nowak’s team concluded that it is equally important to detect changes occurring in normal cells of the tumor niche, because the transformation of these cells stimulates the progression of the disease and contributes to the development of drug resistance.
Melanoma is a malignant neoplasm with a high mortality rate among patients suffering from skin cancer. Despite the use of a number of targeted therapies, patients develop drug resistance quite quickly. One of the factors affecting the effectiveness of cancer therapy is the tumor microenvironment (TME). Solid tumours are made not only of cancer cells, but also of companion cells, such as cancer-associated fibroblasts (CAFs), cancer-associated keratinocytes (CAKs) or adipocytes (CAAs). TME can be a physical barrier that restricts drug access to cancer cells. In addition, surrounding cells adjacent to melanoma cells can stimulate tumor growth and invasive capacity of cancer cells through paracrine signaling, as well as support the process of angiogenesis. Companion cells produce a number of different molecules, including growth factors, cytokines, chemokines, which affect other cells located near them and in distant places in the body. Additionally, surrounding cells can secrete matrix metalloproteases (MMPs), which facilitate tumor cell invasion by degrading extracellular matrix components.
The aim of the research conducted by prof. Dorota Nowak’s team in recent years was to comprehensively study the interactions between cells present in the melanoma niche. This research, funded by the National Science Centre as part of the OPUS project No. 2018/29/B/NZ5/00967, was conducted using co-culture models of melanoma cells of differentiated invasiveness with cells from the microenvironment. The results indicate that:
– cancer-associated fibroblasts derived from normal fibroblasts which cultured with melanoma cells are characterized by an increase in the ability to migrate, invade, proteolysis and express factors regulating the level of matrix metalloproteases. They are also characterized by increased secretion of lactate and pro-inflammatory cytokines and proteins involved in angiogenesis. Changes in CAFs under the influence of melanoma cells were caused mainly by highly invasive tumor lines [1].
– keratinocytes cultured with melanoma cells, on the other hand, showed features of undifferentiated cells (high level of cytokeratin 10), preferring contact with cancer cells rather than with other keratinocytes (reduced level of E-cadherin). CAKs secreted a number of different proteases, including MMP3 and ADAM, which have not been expressed in keratinocytes so far. Activated keratinocytes were also characterized by an increased ability to proteolysis, which was associated with an increase in the level of MMP9 and MMP14 proteases and a decrease in the level of their inhibitors from the TIMP family. In addition, increased ERK kinase activity and increased levels of MMPs regulators – RUNX2 and galectin 3 were observed [2].
– in the case of adipocytes, melanoma cells inhibit the process of adipogenesis, and the fat cells themselves are differentiated into fibroblast-like cells, presenting a fibroblast-like pattern of gelatin digestion and showing increased expression of genes encoding proteins characteristic of fibroblasts. In the studied CAAs, the amount of lipid droplets and the protein that protects them against lipases – perilipin – is reduced. It was also found that the basis of lipolysis occurring in CAAs is an increased ratio of pERK/ERK and pSTAT/STAT proteins compared to normal adipocytes. These cells also secrete more serpin E1 and IL-6 and less CCL2, CXCL1, TIMP-1, TSP-1 than control cells. In addition, CAAs change metabolically – they secrete more lactate and show increased expression of transporters: glucose, lactate and H+ ions [3].
– The cells of the melanoma microenvironment also differentially affect the features associated with its progression. Both fibroblasts, adipocytes and keratinocytes induce increased phosphorylation of the STAT3 protein in cancer cells, which stimulates the progression of melanoma. Melanoma cells cultured with keratinocytes show increased proliferation, while those incubated with fibroblasts and adipocytes are characterized by an increased level of markers of epithelial-mesenchymal transition. All three types of cells (CAFs, CAKs, CAAs) also affect the metabolism of melanoma cells, as evidenced by an increase in the level of glucose transporters GLUT1 and GLUT3 and a decrease in the level of the transporter of various metabolites – MCT-1 [4].
Studies on the interactions between CAAs and cancer cells were also conducted on a cell model of colorectal cancer (CRC) and published in a separate paper [5]. They are financed by another OPUS grant No. 2021/43/B/NZ3/01458, led by Dorota Nowak.
It is worth noting that the research conducted by the Team has also been awarded by the Mayor of Wrocław, who in 2023 awarded the Ludwik Hirszfeld scholarship for the best doctoral students of Wrocław in the field of medical and biological sciences to the doctoral student involved in the project, Ms. Justyna Wądzyńska (supervisor prof. Dorota Nowak). In addition, the team’s previous research on the biology of melanoma has been awarded the award of the Rector of the University of Wrocław and the Rector of the Wroclaw Medical University, as well as the award of the Polish Society of Surgical Oncology.
- Mazurkiewicz J, Simiczyjew A, Dratkiewicz E, Pietraszek-Gremplewicz K, Majkowski M, Kot M, Ziętek M, Matkowski R, Nowak D. Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts. Cell Commun Signal. 2022 May 10;20(1):63. doi: 10.1186/s12964-022-00871-x;
- Mazurkiewicz J, Simiczyjew A, Dratkiewicz E, Kot M, Pietraszek-Gremplewicz K, Wilk D, Ziętek M, Matkowski R, Nowak D. Melanoma stimulates the proteolytic activity of HaCaT keratinocytes. Cell Commun Signal. 2022 Sep 19;20(1):146. doi: 10.1186/s12964-022-00961-w3;
- Simiczyjew A, Wądzyńska J, Pietraszek-Gremplewicz K, Kot M, Ziętek M, Matkowski R, Nowak D. Melanoma cells induce dedifferentiation and metabolic changes in adipocytes present in the tumor niche. Cell Mol Biol Lett. 2023 Jul 22;28(1):58. doi: 10.1186/s11658-023-00476-3;
- Wądzyńska J, Simiczyjew A, Pietraszek-Gremplewicz K, Kot M, Ziętek M, Matkowski R, Nowak D. The impact of cellular elements of TME on melanoma biology and its sensitivity to EGFR and MET targeted therapy. Biochim Biophys Acta Mol Cell Res. 2023 Oct;1870(7):119549. doi: 10.1016/j.bbamcr.2023.119549. Epub 2023 Jul 26.
- Olszańska J, Pietraszek-Gremplewicz K, Domagalski M, Nowak D. Mutual impact of adipocytes and colorectal cancer cells growing in co-culture conditions. Cell Commun Signal. 2023 Jun 14;21(1):130. doi: 10.1186/s12964-023-01155-8.
Date of publication: 20.02.2025
Added by: M.J.
Translated by Zuzanna Łakoma (student of English Studies at the University of Wrocław) as part of the translation practice.
