Growth factors and growth control of heterogeneous cell populations.

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.

journal_name

Bull Math Biol

authors

Michelson S,Leith JT

doi

10.1007/BF02460696

subject

Has Abstract

pub_date

1993-09-01 00:00:00

pages

993-1011

issue

5

eissn

0092-8240

issn

1522-9602

pii

S0092-8240(05)80200-9

journal_volume

55

pub_type

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