Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread
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REVIEW
Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread mucin as the tumor cell receptor G. J. Mizejewski
Received: 18 December 2012 / Accepted: 10 February 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013
Abstract The identification of a tumor cell 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 1983 sparked a series of confirmatory reports which were extended to include multiple tumor types in rats, mice, and humans. The following year, French investigators characterized the binding properties of the AFP receptor but they did not purify and characterize 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, monoclonal antibodies had been raised against the “AFP receptor” derived from breast cancer extracts with claims that the receptor was a widespread oncoprotein biomarker for cancer. To date, that receptor has yet to be identified due to its complex multimeric structure and carbohydrate composition. The present report will review the literature of the multiple AFP receptors previously including their cellular uptake, transmembrane passage, and partial biochemical characterization. . In addition, evidence derived from computer modeling, proteolytic/fragmentation cleavage patterns, domain structure analysis, and protein binding software analysis will be presented in a proposed identification of a widespread protein/gene family of transmembrane proteins which fits many, if not most, of the criteria attributed to the AFP receptor. The proposed receptor protein family is tentatively identified as an epithelial cell surface mucin constituting one (or more) of many classes of single-pass transmembrane proteins. Present data do
G. J. Mizejewski (*) Wadsworth Center, Division of Translational Medicine, New York State Department of Health, Empire State Plaza, Albany, NY 12201, USA e-mail: [email protected]
not support the concept that the AFP receptor is a “universal” tumor receptor and/or biomarker, but rather a widespread mucin protein that functions primarily in protecting and lubricating epithelial mucosal layers, and engaging in signal transduction; the mucin only binds AFP as a molecule serving in a subordinate or ancillary function. Keywords Alpha fetoprotein . Adenocarcinomas . MUC4 . RECAF . Breast cells . Dendritic cells . Mucins . Tumor cells
Introduction Human alpha-fetoprotein (HAFP) is a 67,000 Da glycoprotein consisting of 609 amino acids and 3–5 % carbohydrate– glycan content [1]. HAFP has been found to be an oncofetal protein that is produced during embryonic and fetal development with levels drastically reduced in the perinatal period. Its reappearance in the non-pregnant adult is usually associated with malignant and genetic diseases. With structure similarity to albumin, gc-globulin, and alpha-albumin, HA
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