The invasive capability is fundamental in determining the malignancy of a solid tumor.
Revealing biomedical strategies that are able to partially decrease cancer invasiveness is
therefore an important approach in the treatment of the disease and has given rise to
multiple in vitro and in silico models. We here develop
a hybrid computational framework, whose aim is to characterize the effects of the
different cellular and subcellular mechanisms involved in the invasion of a malignant
mass. In particular, a discrete Cellular Potts Model is used to represent the population
of cancer cells at the mesoscopic scale, while a continuous approach of reaction-diffusion
equations is employed to describe the evolution of microscopic variables, as the nutrients
and the proteins present in the microenvironment and the matrix degrading enzymes secreted
by the tumor. The behavior of each cell is then determined by a balance of forces, such as
homotypic (cell-cell) and heterotypic (cell-matrix) adhesions and haptotaxis, and is
mediated by the internal state of the individual, i.e. its motility. The resulting
composite model quantifies the influence of changes in the mechanisms involved in tumor
invasion and, more interestingly, puts in evidence possible therapeutic approaches, that
are potentially effective in decreasing the malignancy of the disease, such as the
alteration in the adhesive properties of the cells, the inhibition in their ability to
remodel and the disruption of the haptotactic movement. We also extend the simulation
framework by including cell proliferation which, following experimental evidence, is
regulated by the intracellular level of growth factors. Interestingly, in spite of the
increment in cellular density, the depth of invasion is not significantly increased, as
one could have expected.