Leal-Egaña Group Artificial Tumors to Study Cancer Pathologies: Disclosing the Secrets of the Intratumor Heterogeneity at Laboratory Scale

Cancer is one of the deadliest diseases of all time. One reason to explain the high mortality of patients affected by this pathology is the existence of a specific feature characterizing neoplastic cells, known as tumor heterogeneity. Tumor heterogeneity describes the co-localization of malignant cells having multiple geno/phenotypes, in the same tissue. Examples of this heterogeneity are the presence of cells with different morpho-mechanical activity, involving modifications in their sizes and the number of nuclei, to name a couple of examples.¹

Since this variability enables malignant cells to survive chemo-, radio-, and immunotherapies, the possibility to study this process in vitro, mimicking its generation in an environment resembling the biophysical properties of neoplastic tissues, such as the one existing in tumor-like microcapsules.²  This represents a desirable option to find new ways to fight this pathology.

With this purpose in mind, this project is focused on using polymer-based tumor-like microcapsules to mimic the malignant milieu, to determine how the tumor heterogeneity is triggered by biomechanical stress. To accomplish this task, in this research we will be combining biofabrication techniques, with the use of high-throughput analytical strategies, such as Single-Cell RNA-seq and single Cell Traction Force Microscopy, to enable us to characterize the cells at a genetic and biophysical level.

References

1. Leal-Egaña A., et al. (2020). Re-engineering Artificial Neoplastic Milieus: Taking Lessons from Mechano- and Topobiology. Trends in Biotechnology. 38: 142-153. 

2. Antonelli Y., et al. (2024). When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-Like Microcapsules. Advanced Functional Materials. In the press.