Quantifying Impact of Organ-Specific Microenvironment on Cancer Cells
Mentor 1
Mahsa Dabagh
Start Date
10-5-2022 10:00 AM
Description
Cancer is one of the leading causes of deaths worldwide and in 2021 alone, and it accounted for about 10 million deaths. A great deal of effort has been directed toward developing novel therapeutics for different cancer types in the laboratories that do not reach the clinic. The main reason for current limited success in cancer treatment is lack of biologically relevant in vitro or in vivo models resembling the complexity and heterogeneity of tumor microenvironment (TME) observed in patients. Therefore, there is an emerging need for new models to investigate transport of drug particles within TME. TME consists of stromal cells (fibroblasts) within the extracellular matrix (ECM) and Cancer cells (CCs). CCs have also been shown to have a lower Young’s modulus (E). This indicates a higher elasticity, which plays a significant role in determining a cell resistance to deformation, making it a key factor in cellular migration and cancer progression. In this study, we have developed a novel computational model of tumor tissue including CCs, stroma cells (SCs), and ECM. Our main goal is to build an investigational platform to study the crosstalk between CCs, SCs, and ECM. Our results show that heterogeneity of CCs, SCs, and ECM properties, representing different organ-specific biological condition, impact the stresses that CCs experience. This work serves as an important first step in understanding the mechanisms of cancer cell competition with host tissue cells, a process controlling preferential growth of CCs. Our study reveals that cell competition can be controlled by forces that TME exerts on CCs. This work gives a deeper understanding of the cellular interactions within the tumor tissue and these findings have the potential to improve preventable and therapeutic treatments for patients.
Quantifying Impact of Organ-Specific Microenvironment on Cancer Cells
Cancer is one of the leading causes of deaths worldwide and in 2021 alone, and it accounted for about 10 million deaths. A great deal of effort has been directed toward developing novel therapeutics for different cancer types in the laboratories that do not reach the clinic. The main reason for current limited success in cancer treatment is lack of biologically relevant in vitro or in vivo models resembling the complexity and heterogeneity of tumor microenvironment (TME) observed in patients. Therefore, there is an emerging need for new models to investigate transport of drug particles within TME. TME consists of stromal cells (fibroblasts) within the extracellular matrix (ECM) and Cancer cells (CCs). CCs have also been shown to have a lower Young’s modulus (E). This indicates a higher elasticity, which plays a significant role in determining a cell resistance to deformation, making it a key factor in cellular migration and cancer progression. In this study, we have developed a novel computational model of tumor tissue including CCs, stroma cells (SCs), and ECM. Our main goal is to build an investigational platform to study the crosstalk between CCs, SCs, and ECM. Our results show that heterogeneity of CCs, SCs, and ECM properties, representing different organ-specific biological condition, impact the stresses that CCs experience. This work serves as an important first step in understanding the mechanisms of cancer cell competition with host tissue cells, a process controlling preferential growth of CCs. Our study reveals that cell competition can be controlled by forces that TME exerts on CCs. This work gives a deeper understanding of the cellular interactions within the tumor tissue and these findings have the potential to improve preventable and therapeutic treatments for patients.
