CApaCITy · CAncer Stem Cell Imunoreceptors as potential Targets for skin Squamous cell carcinoma
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-09-01 → 2021-08-31
- EU contribution
- €207,312
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
CAncer Stem Cell Imunoreceptors as potential Targets for skin Squamous cell carcinoma
The CAPACITY project revolved around the study of immune receptors present in cancer stem cells as therapeutic targets in skin squamous cell carcinoma. Skin squamous cell carcinoma is one of the most common cancer worldwide. Currently, the treatment options, surgery and radiotherapy procedures are associated with significant patient morbidity, discomfort, and undesirable scarring. On the other hand, the systemic pharmacological treatment available has several side effects, therefore are not a preferred option. The development of a new specific treatment is therefore urgent to treat these patients. Cancer stem cells initiate, sustain the prevalence, and resistance to therapy of skin squamous cell carcinomas. This is a complex process dependent on genetic modification and more interesting determined by the interaction between these cancer cells and the cells present in the tumor microenvironment, in particular macrophages cells. Therefore, the use of therapies able to block these interactions is a promising advance to eradicate skin squamous cell carcinoma. Within the CAPACITY project, using a comprehensive and integrated approach based on human tissues, cell biology, medical chemistry, and advanced technologies, I set the ambitious aim to understand and reveal the role of immune receptors present in cancer stem cells that can be used as therapeutic targets in skin squamous cell carcinoma. The objectives of this Marie Skłodowska Curie Action (MSCA) have been to characterize the presence and the functions of relevant immune receptors in the cancer stem cells in human skin squamous cell carcinomas; 2) Analyzed the relevance of immune receptors as therapeutic targets using new peptide-based inhibitors of protein-protein interactions. The project results revealed that CD99, a membrane protein present in cancer stem cells in skin squamous carcinoma have an impact on the cancer stem cells characteristics and in their connection with macrophages. The analyzed data resulted in new information regarding genes and mechanisms implicated in skin squamous cell cancer. Moreover, peptide-based inhibitors developed in this project may have the potential used in vivo to block squamous cell carcinoma growth.
Data: CORDIS, © European Union
Project objective
Cancer stem cells (CSC) initiate, sustain the prevalence, and resistance to therapy of skin squamous cell carcinomas (SCC). It is well acknowledged that CSC self-renewal and clonal growth is governed by genetic mutations, but also by complex interactions between CSC and the microenvironment. Genetic therapy is difficult to achieve in clinical settings, therefore, targeting cells of the supportive tumor microenvironment is a promising advance to eradicate SCC. Using mouse models of SCC, our previous basic research results uncovered the existence of a direct crosstalk between skin CSC and tumor-associated macrophages (TAM) via Wnt signaling. Interestingly, we observed that Wnt regulated the expression of three CSC receptors, CD99, MFGE8 and Nectin-2, and governed the CSC-TAM crosstalk. Here, I propose to expand this basic research into a translational perspective, to explore the potential of CD99, MFGE8 and Nectin-2 as therapeutic targets for human SCC. There is a major interest in this arena, since the major caveat of targeting Wnt signaling in cancer is the lack of specificity to target CSC, without affecting somatic cells. Moreover, most clinical trials have not been fully efficient to dampen the Wnt response in tumors. Using a comprehensive and integrated approach based on human SCC, cell biology, omics and medical chemistry, along with powerful patient derived xerographs (PDX), my results must likely unearth a role for these immunoreceptors in governing the CSC-TAM crosstalk, and their potential as drug targets for human SSC. This interdisciplinary project will be conducted at the University of Copenhagen (UCPH) in Dr. Perez-Moreno, Dr. Merete Haedersdal, and Dr. Strømgaard groups. Through the CApaCITy project, I will embark in a leading research area with several possibilities to grow into an independent international researcher.
Original text from CORDIS.
Participants
- KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark
Links
Data: CORDIS, © European Union