Feedback regulators in normal and tumour tissues

Abstract

Regulation of cell behaviour and population size is presumed to be not unlike classical regulation in non-biological systems, i.e. it is controlled by the cybernetic principle of negative feedback whereby the performance of progenitor cells depends inversely on a signal from their product, the size of which is proportional to the mass of the product. This signal may be inhibitory, acting directly on the progenitor cells. Alternatively, it may operate via an indirect and integrated inhibitor/stimulator feedback loop in which the one influences the production of the other. Illustrations taken from the various phases of haemopoietic development show the operation of these loops. Haemopoietic stem cells are under the direct influence of both inhibitor and stimulator but it is a feedback signal from the stem cell population that dictates the production of the one rather than the other. A second inhibitor acting at the stem cell level is a low molecular weight tetrapeptide which blocks the entry of cells into DNA synthesis, thus protecting them during a regimen of treatment with an S-phase cytotoxic drug. Proliferation of the maturing cells is also inhibited by feedback products of their fully mature descendants. Here, the effect is one of cell cycle modulation, whereas in the stem cell population the inhibitor and stimulator effect an on/off switch.

Vasohibin‐1 in human breast carcinoma: A potential negative feedback regulator of angiogenesis

“…( 1 ) Negative feedback regulation is considered one of the most important physiological mechanisms with which bodies are endowed, and has been demonstrated to be involved in a wide range of biological phenomena. ( 27 ) This regulation is most effectively performed through the factors produced in endothelial cells but the endothelium‐derived negative feedback regulators of angiogenesis have not been elucidated. Vasohibin‐1 is therefore the first secretory anti‐angiogenic factor from endothelial cells themselves induced by VEGF in EC.…”

Recombinant adenovirus encoding vasohibin prevents tumor angiogenesis and inhibits tumor growth

“…( 24 ) In addition, negative feedback regulation is one of the most important physiological mechanisms of biological organisms and has been shown to control a wide range of phenomena. ( 25 ) However, to date, no such regulators have been established for the regulation of angiogenesis.…”

Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis

“…Negative feedback regulation is one of the most important physiological mechanisms with which bodies are endowed, and has been demonstrated to control a wide range of phenomena (15). However, no such regulators have been established for the regulation of angiogenesis to date.…”