HOST RESPONSE IN TUMOR-GROWTH AND PROGRESSION

Tumor growth and progression result from complex controls that appear to be facilitated by the growth factors (GFs) which emerge from the tu mor and find responsive targets both within the tumor and in the surro unding host. For example, basic fibroblast growth factor (bFGF) and va scular endothelial growth factor (VEGF) are both angiogenic signals wh ich appear to emerge from upregulated genetic messages in the prolifer ating rim of a solid tumor in response to tumor-wide hypoxia. If these signals are generated in response to unfavorable environmental condit ions, i.e. a tumor-wide decrease in oxygen tension, then the tumor may be playing a role in manipulating its own environment, Two questions are raised in this paper: (1) How does the host respond to such signal s? (2) Is there a linkage between the host's response and the ultimate growth of the tumor? To answer these questions, we have idealized the se adaptive signals within a mathematical model of tumor growth. The h ost response is characterized by a function which represents the host' s carrying capacity for the tumor, If the function is constant, then e nvironmental control is strictly limited to tumor shape and mitogenic signal processing, However, if we assume that the response of the loca l stroma to these signals is an increase in the host's ability to supp ort an ever larger tumor, then the model describes a positive feedback controller, In this paper, we summarize our previous results and ask the question: What form of host response is reasonable, and how will i t affect ultimate tumor growth? We examine some specific candidate res ponse functions, and analyze them for system stability, In this model, unstable states correspond to 'infinite' tumor growth, We will also d iscuss countervailing negative feedback signals and their roles in mai ntaining tumor stability.