Copyright © Bojana Gligorijevic. All rights reserved.
Invadopodia in vivo (Publications) are essential for intravasation and subsequent metastasis in breast carcinoma. Utilizing top-down approach to imaging metastasis, we recently demonstrated the context-dependency of invadopodia and extracellular matrix degradation via SVM classification of tumor cell phenotypic patterns in mouse models. Namely, switching between different motility strategies (protease-dependent/independent) can not be explained or predicted by measurements of a single parameter such as extracellular matrix or growth factor levels. A number of mechanical and chemical microenvironment signals and their non-linear, complex interactions in fact drive tumor cell decisions. As a result, cancer cells can reach the same phenotype through several different paths. We are currently interested in recapitulating phenotypic switching utilizing bottom-up platforms such as organs-on-a-chip, bioprinted tissue and microfluidic platforms is essential for development of next-generation of early-metastasis diagnostic tests and therapeutic targets.
When assuming the same genetic make-up, phenotypes available to any cancer cell throughout its lifetime, include proliferation, necrosis/apoptosis, motility, dormancy, autophagy. Similarly to different motility strategies, phenotypic switching can transiently occur between any of these behaviors under certain regimes. It is our goal to discover regimes which lead cancer cells to change their behavior and be able to control them. Such a possibility would allow for example, to develop therapeutics which drive cancer into apoptosis without the need for drug internalization.