Update of Alpha Fetoprotein Growth-Inhibitory Peptides as Biotherapeutic Agents for Tumor Growth and Metastasis

Abstract

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.

Role for estradiol in female-typical brain and behavioral sexual differentiation

“…By contrast, both Uriel et al [101] and Arnon et al [4] showed that human AFP could actually bind estrogens. In either case, human AFP-derived peptides are able to display some anti-estrogenic activity [14,66,102]. These AFP-derived peptides are currently under investigation as potential agents for treating estrogen-dependent breast cancers and other tumors [13,66].…”

“…In either case, human AFP-derived peptides are able to display some anti-estrogenic activity [14,66,102]. These AFP-derived peptides are currently under investigation as potential agents for treating estrogen-dependent breast cancers and other tumors [13,66]. Finally, it is not known if a protection from maternal estrogens is actually required since the reigning idea is that in humans, androgens, not estrogens, are the primary cause of brain masculinization (reviewed in [107]).…”

Cancer, circulating tumor cells, and metastasis: could protein-derived peptide fragments impede brain metastases?

“…Other sets of data involving AFP-derived peptides have been generated in vitro involving cancer cell adhesion, cell-to-cell interactions, cell spreading, motility, migration, and growth [32,33] . Regarding cancer cell proliferation, GIP was found to inhibit growth in multiple BC cell lines in vitro and to inhibit cell-tocell contact inhibition overgrowth in cultured MCF-7 cells [33][34][35] .…”

“…The final involvement of GIP with cancer cell activities was demonstrated using in vivo models of human BC xenografts in mice. GIP was reported to suppress cancer growth/proliferation in both xenograft and homograft models of MCF-7, GI-101, MDA-MB-231, and 6WI-1 BC tumors in host mice [25,32] . In the human MDA-MB-231 BC in vivo mouse model, GIP injections resulted in a 3-fold reduction in BC metastasis to the lungs as compared to controls.…”

Hemoglobin-associated proteins isolated from blood serum of Ehrlich carcinoma-bearing mice

“…AFP acts as a growth factor and biological response modifier, which affects cell proliferation (9)(10)(11)(12). AFP functions as a transporter of various ligands, such as steroid hormones and hemoglobin degradation products (bilirubin) (13)(14)(15). Ivanov et al (16,17) reported that peptides resulting from hemoglobin degradation products affect tumor cell proliferation.…”