Mathematical modelling of cancer invasion: Phenotypic transitioning provides insight into multifocal foci formation

TL;DR

This paper introduces a new mathematical model to study how phenotypic switching in cancer cells influences tumor invasion and multifocal spread, providing insights into disease progression and potential prognosis.

Contribution

The paper develops a novel mathematical model incorporating phenotypic plasticity to explain multifocal tumor formation and invasion dynamics.

Findings

Phenotypic plasticity is crucial for tumor invasion.

Model simulations replicate multifocal breast carcinoma patterns.

Tumor cell plasticity impacts disease progression.

Abstract

The transition from the epithelial to mesenchymal phenotype and its reverse (from mesenchymal to epithelial) are crucial processes necessary for the progression and spread of cancer. In this paper, we investigate how phenotypic switching at the cancer cell level impacts on behaviour at the tissue level, specifically on the emergence of isolated foci of the invading solid tumour mass leading to a multifocal tumour. To this end, we propose a new mathematical model of cancer invasion that includes the influence of cancer cell phenotype on the rate of invasion and metastasis. The implications of model are explored through numerical simulations revealing that the plasticity of tumour cell phenotypes appears to be crucial for disease progression and local invasive spread. The computational simulations show the progression of the invasive spread of a primary cancer reminiscent of in vivo multifocal breast carcinomas, where multiple, synchronous, ipsilateral neoplastic foci are frequently observed and are associated with a poorer patient prognosis.