  Complex tumor-host interactions can significantly affect the growth dynamics
and morphologies of progressing neoplasms. The growth of a confined solid tumor
induces mechanical pressure and deformation of the surrounding
microenvironment, which in turn influences tumor growth. In this paper, we
generalize a recently developed cellular automaton model for invasive tumor
growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS
Comput. Biol. 7, e1002314 (2011)] by incorporating the effects of pressure.
Specifically, we explicitly model the pressure exerted on the growing tumor due
to the deformation of the microenvironment and its effect on the local
tumor-host interface instability. Both noninvasive-proliferative growth and
invasive growth with individual cells that detach themselves from the primary
tumor and migrate into the surrounding microenvironment are investigated. We
find that while noninvasive tumors growing in "soft" homogeneous
microenvironments develop almost isotropic shapes, both high pressure and host
heterogeneity can strongly enhance malignant behavior, leading to finger-like
protrusions of the tumor surface. Moreover, we show that individual invasive
cells of an invasive tumor degrade the local extracellular matrix at the
tumor-host interface, which diminishes the fingering growth of the primary
tumor. The implications of our results for cancer diagnosis, prognosis and
therapy are discussed.
