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 tumor and find responsive targets both within the tumor and in the surrounding host. For example, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are both angiogenic signals which appear to emerge from upregulated genetic messages in the proliferating rim of a solid tumor in response to tumor-wide hypoxia. If these signals are generated in response to unfavorable environmental conditions, 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 signals? (2) Is there a linkage between the host's response and the ultimate growth of the tumor? To answer these questions, we have idealized these adaptive signals within a mathematical model of tumor growth. The host response is characterized by a function which represents the host's carrying capacity for the tumor. If the function is constant, then environmental control is strictly limited to tumor shape and mitogenic signal processing. However, if we assume that the response of the local stroma to these signals is an increase in the host's ability to support 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 it affect ultimate tumor growth? We examine some specific candidate response functions, and analyze them for system stability. In this model, unstable states correspond to 'infinite' tumor growth. We will also discuss countervailing negative feedback signals and their roles in maintaining tumor stability.
Michelson
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Research Support and Information Services, Roche Bioscience, Palo Alto, CA 94303, USA. seth.michelson@roche.com
Leith
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JT
D000818:Animals; D002455:Cell Division / Q000502:physiology; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008222:Lymphokines / Q000502:physiology; D008432:Mathematical Computing; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2