Approximately 90% of cancer-related deaths arise due to secondary metastases rather than from the typically less aggressive primary tumours they originate from. Hence it is crucial to understand the mechanisms of metastatic spread.
In particular, the roles of mesenchymal-like versus epithelial-like cancer cell phenotypes and, closely linked to this, of collective invasion by circulating tumour cell clusters versus single cell invasion are currently actively investigated.
To shed light on the metastatic process, I developed a spatially explicit hybrid individual-based model, in which mesenchymal- and epithelial-like cancer cell phenotypes undergo persistent spontaneous motion via diffusion as well as directed movement in response to gradients of the extracellular matrix (ECM) density, as derived from an underlying reaction-diffusion-taxis partial differential equation (PDE). These gradients in ECM density are in turn caused by two types of matrix degrading enzymes (MDEs)—the membrane-bound MT1-MMP and the diffusive MMP2—both of which are expressed by the mesenchymal-like cancer cells. In contrast to the cancer cells and the membrane-bound Mt1-MMP, ECM and MMP-2 evolve in a continuous manner, which makes this a hybrid model.
The model’s simulations are run in the form of a cut through a small avascular tumour. We use four square grids—one to represent the primary site and three to show the secondary site’s dynamics. If cells invade far enough into the ECM, they may intravasate into the circulation via vessels that are spread throughout primary tumour site’s grid. This way, both tumour cell clusters and single tumour cells circulate in the blood stream with the potential to extravasate at the secondary sites throughout the body, where they may exist as dormant disseminated cancer cells or grow into micrometastases.
Our aim is to provide a framework to model the interlinked processes of cancer cell invasion and metastatic spread in a spatially explicit manner. Further, we investigate the relative effectiveness and likelihood of metastatic spread mediated by single cancer cells vs. cell clusters, and to explore the influence of the relative abundance of mesenchymal and epithelial cancer cell phenotypes on the metastatic outcome.