Periodic Reporting for period 1 - GlyCANswer (Decoding the Cancer Glycoproteome Driven Immune Response)
Período documentado: 2019-05-15 hasta 2021-05-14
In this project various complementary methods for the analysis of the glycosylation of cancer cells were applied to provide a comprehensive characterization of the cancer cells. In addition, a completely new method to analyze glycoproteins produced by cancer cells was established yielding new insights into the cancer biology.
The glycosylation of cancer cells was analyzed using various complementary approaches such as lectin and antibody stainings which were used to quantify the specific glycan-epitopes on cancer cells. In addition, cancer cells were analyzed using state-of-the-art glycoproteomics to get a complete overview on the cancer cell glycosylation. Lastly, gene expression analysis was performed to provide an understanding of changes in the glycosylation machinery of cancer cells that led to the formation of measured glycan-epitopes and glycoproteins.
2. Mechanisms of immune regulation have been studied.
The glycosylation of cancer cells was altered through genetic and pharmacologic approaches. These cancer cells were then compared with their unaltered cancer cells on their capacity to change the anti-cancer immune response. The results provided a deeper understanding how cancer cell glycosylation controls the immune system and contributes to the aggressive progression of tumors.
3. A glycan-binding protein library has been established for an improved analysis of the glycosylation in diseases
A lectin (glycan-binding protein) library consisting of more than 130 mammalian lectins, many of which are key components of the immune system, has been produced and used to study diseases. As first proof of concept, these lectins have been used to identify new SARS-CoV-2 binding proteins. These findings have been published in a peer-reviewed open-access journal: https://doi.org/10.15252/embj.2021108375
4. New methods have been established to assess breast cancer alterations.
A new method to assess the glycoprotein produced by breast cancer cells has been rigorously established and optimized. The method allowed to assess with an unprecedented detail the analysis of cancer cell glycoproteins. This new data builds the foundation for future studies that will be published in open access papers and disseminated in the future.
No website has been developed for the project.
Lastly, new methods that can be employed for the analysis of cancer glycosylation have been developed. These methods will be further improved and used in the future to gather unprecedentedly detailed information on the malignant process taking place in a tumor. Also this method holds promise to catalyze future ambitions to develop new treatments and identify new biomarkers for cancer and may thereby improve the outcome of cancer patients around the globe.