Growth-Regulative Activity of Human Alpha-Fetoprotein for Different Types of Tumor and Normal Cells

Abstract

The dose-dependent α-fetoprotein (AFP) reactivity of different types of tumor cells and normal embryonal fibroblasts, which are capable of taking up AFP, was investigated. High doses (more than 100 µg/ml) of purified human AFP were shown to induce strongly dose-dependent growth inhibition of human hepatoma HepG2 cells, human lymphoblastoma MT4 cells, lymphoma Jurkat cells and murine fibroblastoma L929 cells. Human mammary carcinoma MCF-7 cells also revealed a growth inhibitory response to AFP, although to a lesser extent. Equivalent doses of human serum albumin (HSA) demonstrated no effect on these cells. On the contrary, normal embryonal fibroblasts of different organ origin showed dose-dependent stimulation (50–90%) of proliferation in response to AFP. A similar stimulative effect was obtained when embryonal fibroblasts were treated with the same doses of HSA. The myeloblastoma cell line U-937 and the normal epidermal fibroblast cell line M19 were shown to be resistant to the AFP action over a wide range of protein concentrations. It was demonstrated that growth factor deprivation (i.e. low serum concentration) could stimulate U-937 cell proliferation in response to high doses of AFP. It was also shown that intensive washing of U-937 and MCF-7 cells with fresh medium to remove secreted cytokines and growth factors distinctly increased cell sensitivity to high-dose-AFP-induced growth-inhibitory activity. Low AFP concentrations (less than 100 µg/ml) failed to induce growth inhibition in all studied cells and rather showed a slight stimulative effect. These findings demonstrate that physiological levels of AFP can exhibit a dose-dependent growth-regulatory activity toward sensitive tumor or developing cells. Our data demonstrated that AFP could reveal either stimulative or inhibitory growth activity, depending on the relative concentration of AFP and on exogenous or endogenous cytokines and growth factors in the cell culture medium. A growth-stimulative activity in normal embryonal fibroblasts and certain tumor cell lines exhibited by low AFP concentrations is supposed to result from the synergistic effects of AFP and various other secreted growth factors.

High α‐fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and β‐catenin mutations

“…This suggestion is in agreement with recent observations that AFP can act as a growth regulator under certain circumstances. Increased proliferation in vitro in response to AFP has been observed for developing or embryonic cells, 15,18 mouse and human hepatoma cells, 17 but not the untransformed cells because of the absence of specific membrane AFP receptors. 45 The AFP-enhanced proliferation could be diminished by anti-AFP antibody.…”

Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells

“…When treated with AFP, the two oncogenes in Bel 7402 cells express promptly, thereafter the expression of these oncogenes dramatically declines. Previous researches had showed that AFP promoted the proliferation [1][2][3][4][5][6] and some oncogene expression of many tumor cells [15,16] . Cell growth was regulated by various factors, in which, some oncogene coding proteins have an important function in modulating growth and differentiation of the cells.…”

“…AFP always accompanies with the growth of liver cells, and it is possible that AFP may be related to the proliferation of tumor or fetal cells. Some investigations had showed that AFP could be individually synergy with other growth factors to promote the growth of many tumor or normal cells [1][2][3][4][5][6] . Alpha-fetoprotein (MW 69 ku) is a kind of biomacromolecules, and it is impossible to directly permeate the cells to regulate cell proliferation.…”

Computational Design and Experimental Discovery of an Antiestrogenic Peptide Derived from α-Fetoprotein

“…4 AFP is a growth-regulating hormone with the capacity to stimulate or inhibit growth. 5 From fertilization through birth, AFP holds an important physiological role as a developmental promoter for the fetus. More recent reports have shown that AFP has antiestrogenic activity and can inhibit the growth of estrogen dependent cancer.…”