Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family.

The identification of a receptor for alpha-fetoprotein (AFP) has long been sought in the field of medicine. The uptake and endocytosis of AFP by rat tumor cells in 1984 sparked a series of confirmatory reports and the original studies were then extended to include multiple tumor types in rats, mice, and humans. The following year, French investigators partially characterized the binding properties of the AFP receptor, but they were not able to purify the receptor. It was not until 1991-1992 that an AFP receptor was partially purified and characterized from both human monocytes and breast cancer cells. By 1993, a monoclonal antibody had been raised against the AFP receptor produced from a breast cancer extract with claims that the receptor was a widespread (universal) oncofetal biomarker for cancer. However, that receptor has yet to be cloned and/or purified due to its complex multimeric binding interactions and associations. The present report will review the literature of the multiple putative AFP receptors described to date, the cellular uptake and endocytosis of AFP, and the biochemical characterization of these putative cell-surface proteins. In addition, evidence derived from computer modeling, proteolytic degradation patterns, and amino acid sequence analysis will be presented in a proposed identification of a family of multi-ligand binding receptors; this family fits many, if not most, of the criteria required for an AFP receptor. The purposed receptor protein family is tentatively identified as the Scavenger receptors which comprise several classes of single- and double-pass integral transmembrane proteins. Present data do not support the concept that the AFP receptor is a "universal" tumor receptor and/or biomarker.