Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy.
alpha-fetoprotein has long been considered the 'gold-standard' in the field of tumor markers. During the several decades since the recognition of mammalian alpha-fetoprotein as a tumor-associated fetal protein, it has been purified, characterized, cloned and sequenced for use in the clinical diagnostic laboratory. However, the biological role of alpha-fetoprotein in the regulation of cancer growth has received comparatively little attention. Only during the last decade has the modulatory role of alpha-fetoprotein in neoplastic growth been realized and implemented in experimental models. This review examines the basis for the current consensus that alpha-fetoprotein does indeed regulate neoplastic growth through the presence of an alpha-fetoprotein cell surface receptor that undergoes internalization to the cell interior. Studies involving uptake of this fetal protein have since culminated in radio imaging reports as well as the use of alpha-fetoprotein as an anticancer drug conjugate. Finally, the therapeutic utilization of alpha-fetoprotein and its peptidic fragments as growth-response modifiers encompasses biological events, such as apoptosis G-coupled signal transduction, gene therapy, vaccination and cancer chemoprevention.
Mizejewski
Gerald J
GJ
Division of Molecular Medicine, Wadsworth Center for Laboratory and Research, NYS Health Dept., Empire State Plaza, Albany, NY 02201, USA.
D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D011401:Promoter Regions, Genetic; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*
D019138:Antibodies, Blocking; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D000509:alpha-Fetoproteins; C042144:alpha-fetoprotein receptor, human; D019204:GTP-Binding Proteins