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Biophysically and molecularly defined 3D in vitro skin cancer model
In the past few years, there has been significant progress in developing 3D in vitro cancer models. These models serve as a link between 2D cell culture models and in vivo xenograft mouse models, which are considered the gold standard in cancer research and preclinical drug assessment. Various 3D methods have been explored, and among them, spheroids have shown great potential as an alternative to traditional methods. These are often used in a scaffold-free context lacking the physical environment and interactions present in vivo. Therefore, scaffold-based approaches have gained more attention due to their ability to mimic the tumor microenvironment (TME), which is a crucial factor in tumor behavior. By providing a scaffold that mimics the TME, we can gain a better understanding of the influence of TME on tumor spheroid behavior and drug response.
This project aims to establish a 3D scaffold-based spheroid tumor model that mimics the behavior of human squamous cell carcinoma (SCC) at varying degrees of aggressiveness. The model will be designed to replicate the tumor and its microenvironment using a molecular and biophysical defined system. The ultimate objective is to create optimized models that have a physiological similarity to human SCC, which can enhance overall knowledge and increase the predictive value, enabling preclinical-to-clinical translation. By doing this, we hope to provide a 3D in vitro model that can reduce and potentially replace the use of animal models as whenever possible.
Keywords: 3D, alginate, hydrogels, in vitro models, tissue engineering, tumor microenvironment, spheroids, skin cancer
To mimic the solid tumor component, we use established spheroid models to produce tumor spheroids from two different cell lines. The proposed cell types, the human A431 cell line and the human SCC-13 cell line, are both human epidermoid carcinoma cell lines used in skin cancer research. They differ in their malignancy, with the A431 cell line being more malignant, allowing us to study specific tumor development based on aggressiveness and related stage. The tumor spheroids will be added to the model by encapsulating the spheroids in a defined hydrogel scaffold. Spheroid behavior of both cell types in different hydrogel conditions will be investigated and compared between the cell types. To determine the importance of the different scaffold parameters for the development of the spheroids in the 3D scaffold, the spheroids will be closely monitored through imaging and immunofluorescent staining. To further analyze the performance and significance of the scaffold parameters on tumor spheroid behavior protein analysis will be conducted. The protein analysis of tumor spheroids will complement immunofluorescent readouts and help to characterize cell types and particular changes in response to scaffold parameters.
To mimic the solid tumor component, we use established spheroid models to produce tumor spheroids from two different cell lines. The proposed cell types, the human A431 cell line and the human SCC-13 cell line, are both human epidermoid carcinoma cell lines used in skin cancer research. They differ in their malignancy, with the A431 cell line being more malignant, allowing us to study specific tumor development based on aggressiveness and related stage. The tumor spheroids will be added to the model by encapsulating the spheroids in a defined hydrogel scaffold. Spheroid behavior of both cell types in different hydrogel conditions will be investigated and compared between the cell types. To determine the importance of the different scaffold parameters for the development of the spheroids in the 3D scaffold, the spheroids will be closely monitored through imaging and immunofluorescent staining. To further analyze the performance and significance of the scaffold parameters on tumor spheroid behavior protein analysis will be conducted. The protein analysis of tumor spheroids will complement immunofluorescent readouts and help to characterize cell types and particular changes in response to scaffold parameters.
The primary objective of the project is to investigate the behavior of a less malignant SSCC-13 cell line in the current established 3D scaffold, and compare it to the behavior observed for the more malignant A431 cell line. The main tasks here include
- cell culture/ spheroid culture
- cell/spheroid encapsulation in 3D hydrogels
- 3D hydrogel optimization
- Immunofluorescent staining
- Fluorescent widefield microscopy/ confocal laser scanning microscopy
- Protein extraction/ Western Blotting
The primary objective of the project is to investigate the behavior of a less malignant SSCC-13 cell line in the current established 3D scaffold, and compare it to the behavior observed for the more malignant A431 cell line. The main tasks here include
- cell culture/ spheroid culture - cell/spheroid encapsulation in 3D hydrogels - 3D hydrogel optimization - Immunofluorescent staining - Fluorescent widefield microscopy/ confocal laser scanning microscopy - Protein extraction/ Western Blotting
If you are interested, please contact me Gabriela Da Silva André (dasilvga@ethz.ch) with a short CV and transcript of records. The focus of the project can be adjusted to the student’s interest and experience.
If you are interested, please contact me Gabriela Da Silva André (dasilvga@ethz.ch) with a short CV and transcript of records. The focus of the project can be adjusted to the student’s interest and experience.