Review of Growth Inhibitory Peptide as a biotherapeutic agent for tumor growth, adhesion, and metastasis.
This review surveys 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 full length 590 amino acid AFP molecule. The GIP has been shown to be growth-suppressive in both fetal and tumor cells but not in adult terminally-differentiated cells. The mechanism of action of this peptide has not been fully elucidated; however, GIP is highly interactive at the plasma membrane surface in cellular events such as endocytosis, cell contact inhibition and cytoskeleton-induced cell shape changes. The GIP was shown to be growth-suppressive in nine human tumor types and to suppress the spread of tumor infiltrates and metastases in human and mouse mammary cancers. The AFP-derived peptide and its subfragments were also shown to inhibit tumor cell adhesion to extracellular matrix (ECM) proteins and to block platelet aggregation; thus it was expected that the GIP would inhibit cell spreading/migration and metastatic infiltration into host tissues such as lung and pancreas. It was further found that the cyclic versus linear configuration of GIP determined its biological and anti-cancer efficacy. Genbank amino acid sequence identities with a variety of integrin alpha/beta chain proteins supported the GIP's linkage to inhibition of tumor cell adhesion and platelet aggregation. The combined properties of tumor growth suppression, prevention of tumor cell-to-ECM adhesion, and inhibition of platelet aggregation indicate that tumor-to-platelet interactions present promising targets for GIP as an anti-metastatic agent. Finally, based on cholinergic studies, it was proposed that GIP could influence the enzymatic activity of membrane acetylcholinesterases during tumor growth and metastasis. It was concluded that the GIP derived from full-length AFP represents a growth inhibitory motif possessing instrinsic properties that allow it to interfere in cell surface events such as adhesion, migration, metastasis, and aggregation of tumor cells.
Muehlemann
M
M
Serometrix Biotechnology, Syracuse, NY, USA. Muehlemann@illuminationtech.com
Miller
K D
KD
Dauphinee
M
M
Mizejewski
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D001688:Biological Products / Q000627:therapeutic use*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D004705:Endocytosis; D006131:Growth Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D010974:Platelet Aggregation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000627:therapeutic use*
D001688:Biological Products; D006131:Growth Inhibitors; D010455:Peptides; D000509:alpha-Fetoproteins