Update of alpha fetoprotein growth-inhibitory peptides as biotherapeutic agents for tumor growth and metastasis.
The present update describes the biological activities of an alpha fetoprotein (AFP)-derived peptide termed the growth-inhibitory peptide (GIP), which is a synthetic 34-amino acid segment produced from the native molecule. The GIP has been shown to be growth-suppressive in both fetal and tumor cells but not in adult cells. Even though its mechanism of action has not been completely elucidated, GIP has been shown to engage in cellular events such as endocytosis, cellular aggregation, hemagglution, and cytoskeleton-induced cell shape changes. The GIP was shown to be growth-suppressive in nine different human tumor types and to suppress the spread of tumor infiltrates and metastases in human and mouse mammary cancers. It was further found that the oligomeric state (cyclic vs. linear configuration) of the GIP determined its biological and anticancer efficacy. The combined properties of tumor growth suppression and reduction of tumor metastases represent promising areas for GIP as a chemotherapeutic agent. It was concluded that the GIP derived from full-length AFP represents a growth-inhibitory motif possessing intrinsic properties that allow it to interact in cell surface events such as tumor proliferation, progression, and metastasis.
Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA. Mizejew@wadsworth.org
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Muehlemann
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Dauphinee
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001201:Ascites / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014183:Transplantation, Heterologous; D000509:alpha-Fetoproteins / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010446:Peptide Fragments; D000509:alpha-Fetoproteins