CANCER CELL MIGRATION

Principal Investigator

Staff

Research topic

Cell dynamics in cancer progression: exploiting patient-derived tumors organoids to unveil cancer phenotypic intra-tumor heterogeneity

Background

Phenotypic heterogeneity of cells within tumors has been well known for a long time and recent high-resolution genome-wide studies have revealed genetic heterogeneity within individual cancers as well. Non-genetic sources of phenotypic heterogeneity are attributable to transcriptional differences that can be mapped to differentiation hierarchies which lead to substantial cell-to-cell variability. It is now evident that intra-tumor phenotypic heterogeneity, and especially aspects related to clonal diversity and differentiation, has to be considered to build a valid experimental model and to design rational therapeutic approaches. Indeed intra- and inter-tumor heterogeneity, in terms of cellular metabolism, motility, senescence, proliferation and differentiation profoundly affects tumor progression and consequently the response to drugs. Our aim is to investigate tumor phenotypic heterogeneity by studying cell dynamics in organoids and 3D cellular models.

Research achievements

During the last years, we have been working on the development of new three-dimensional culture systems that in combination with conventional cell biology approaches, can help understanding tumor cell dynamics from several points of view. 

We reported a new model for in vitro tumor angiogenesis studies based on the ex-vivo culture of mouse aorta. With this 3D model we have been able to discover the role of the endothelial podosomes, in tumor angiogenesis. Moreover, new molecular and biological mechanisms regulating collective migration in cancer have been described exploiting 3D cell spheroids.

Now we have established large collections of patient-derived organoids from colorectal, breast and lung cancer.  

Conclusions and perspectives

3D culture and organoids are great models to study tumor cell dynamics and intra-tumor heterogeneity.  Exploiting these models we are investigating pivotal mechanisms of cancer progression, such as cell migration, metabolic reprogramming, cellular senescence and differentiation. 

We are convinced that a combination of large scale screening techniques and of more traditional cell biology approaches will prove beneficial to gain insights into tumor progression and into a rational design of therapeutic approaches. 

Publications

At this link, you can find all the scientific publications of the Principal Investigator.