Growth factors and growth control of heterogeneous cell populations |
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Authors: | Seth Michelson John T Leith |
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Institution: | (1) Department of Biomathematics, Scientific Information Department, Syntex Research, Drug Discovery, M/S A4-100, 3401 Hillview Avenue, 94303 Palo Alto, CA, U.S.A.;(2) Department of Radiation Medicine, Brown University, Box G-B004, 02912 Providence, RI, U.S.A. |
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Abstract: | In an earlier work a model of the autocrine and paracrine pathways of tumor growth control was developed (Michelson and Leith.
1991. Autocrine and paracrine growth factors in tumor growth.Bull. math. Biol.
53, 639–656). The target population, a generic tumor, was modeled as a single, homogeneous population using the standard Verhulst
equation of logistic growth. Mitogenic signals were represented by modifications to the Malthusian growth parameter and adaptational
signals were represented by modifications to the carrying capacity. Three growth scenarios were described: (1) normal tissue
wound healing, (2) unperturbed tumor growth, and (3) tumor growth in a radiation damaged environment, a phenomenon termed
the Tumor Bed Effect (TBE).
In this paper, we extend those results to include a “triad” of growth factor controls (autocrine, paracrine and endocrine)
and heterogeneity of the target population. The heterogeneous factors in the model represent either intrinsic, epigenetic
or environmental differences in both normally differentiating tissues and tumors.
Three types of growth are modeled: (1) normal tissue differentiation or wound healing, assuming no communication between differentiated
and undifferentiated cell compartments; (2) normal wound healing with feedback inhibition, due to signalling from the differentiated
compartment; and (3) the development of hypoxia in a spherical tumor. The signal processing within the triad is discussed
for each model and biologically reasonable constraints are defined for limits on growth control. |
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