Elaboration of a multispecies model of solid tumor growth with tumor-host interactions

Abstract

There has been increasing evidence of the critical effects of microenvironmental influence on tumor growth and metastasis. In this report, we extend a multispecies continuum model of solid tumor growth to include interaction of the tumor with its microenvironment. This new model, which incorporates reported interactions between tumor-and stroma-derived chemical signals, predicts a nonlinear response to host factors: increased growth and asymmetry of the tumor at low levels of stromal fibroblast-produced Hepatocyte Growth Factor / Scatter Factor (HGF/SF), and reduced growth at high levels.We test the model predictions using colon cancer initiating cell (CCIC) spheroids grown in media in varying concentrations of HGF. The experiments show qualitatively similar behavior to the model predictions. We plan to use the experimental studies to calibrate the mathematical model, and to use the mathematical model to make predictions regarding tumor behavior in order to guide future experimental studies.