Could a Growth Inhibitory Factor, Present Only during Pregnancy, be Made Available to Treat Cancer in Adults? A Commentary

Human alpha-fetoprotein (AFP) is well-known as the “gold standard” biomarker for liver and germ cell tumors. It has also been utilized as a pregnancy screening analyte for neural tube defects as well as Down syndrome, when combined with other gestational-age dependent biomarkers. However, a lesser known and recognized property of AFP is its role in the maintenance and monitoring of fetal growth during ontogenetic development in man. Although a major function of AFP during pregnancy involves the serum transport of estrogens, fatty acids, retinoid, and other compounds, the positive and negative regulation of fetal growth is a vital additional function of AFP. Human AFP largely functions as a growth promoting agent; however, the fetal protein is able to temporarily convert to a growth inhibitory factor in stress and shock environments in the fetal milieu. The development of a transient form of AFP or its derived peptides could be harnessed for use as an adjunct therapeutic agent to treat cancer in adults.

New Proteins Found Interacting with Brain Metallothionein-3 Are Linked to Secretion

Metallothionein 3 (MT-3), also known as growth inhibitory factor (GIF), exhibits a neuroinhibitory activity. Our lab and others have previously shown that this biological activity involves interacting protein partners in the brain. However, nothing specific is yet known about which of these interactions is responsible for the GIF activity. In this paper, we are reporting upon new proteins found interacting with MT-3 as determined through immunoaffinity chromatography and mass spectrometry. These new partner proteins—Exo84p, 14-3-3 Zeta,αandβEnolase, Aldolase C, Malate dehydrogenase, ATP synthase, and Pyruvate kinase—along with those previously identified have now been classified into three functional groups: transport and signaling, chaperoning and scaffolding, and glycolytic metabolism. When viewed together, these interactions support a proposed model for the regulation of the GIF activity of MT-3.