Quantitative aspects of autocrine regulation in tumors.

Autocrine regulation is defined as a mechanism of self-control in growth and differentiation; this mode of regulation among histologically homologous cells is mediated humorally. Autocrine mechanisms involve: 1. Autonomously controlled production and secretion of autocrine mediators. 2. Distribution of autocrine mediators among cells. 3. Expression by cells of functional receptors for autocrine mediators. 4. Transduction and intracellular integration of signals mediated by autocrine mediators. 5. Growth response. 6. Maintenance of autonomous control of growth and/or differentiation state in the progeny Biochemical and biological evidence for most of these steps in various transformed cells makes it possible to analyze autocrine control as a multifaceted process. This process depends on tumor cellularity and histoarchitecture, on time and on external influences on secretion of autocrine mediators (e.g., estrogens in estrogen-dependent breast cancer). We review the quantitative aspects of experimental evidence for autocrine control in tumors and examine the phenomenological and some mechanistic concepts in creating integrative, quantitative, and experimentally verifiable mathematical models of autocrine regulation.