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Apolipoprotein E: A potent inhibitor of endothelial and tumor cell proliferation
Author(s) -
Vogel Tikva,
Guo NengHua,
Guy Rachel,
Drezlich Nina,
Krutzsch Henry C.,
Blake Diane A.,
Panet Amos,
Roberts David D.
Publication year - 1994
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240540306
Subject(s) - cell growth , apolipoprotein e , basic fibroblast growth factor , angiogenesis , endothelial stem cell , biology , cell culture , microbiology and biotechnology , growth factor , chemistry , cancer research , medicine , biochemistry , receptor , in vitro , genetics , disease
Recombinant human apolipoprotein E3 (apoE), purified from E. coli , inhibited the proliferation of several cell types, including endothelial cells and tumor cells in a dose‐ and time‐dependent manner. ApoE inhibited both de novo DNA synthesis and proliferation as assessed by an increase in cell number. Maximal inhibition of cell growth by apoE was achieved under conditions where proliferation was dependent on heparin‐binding growth factors. Thus, at low serum concentrations (0–2.5%) basic fibroblast growth factor (bFGF) stimulated the proliferation of bovine aortic endothelial (BAE) cells severalfold. The bFGF‐dependent proliferation was dramatically inhibited by apoE with an IC 50 ≈ 50 nM. Under conditions where cell proliferation was mainly serum‐dependent, apoE also suppressed growth but required higher concentrations to be effective (IC 50 ≈ 500 nM). ApoE also inhibited growth of bovine corneal endothelial cells, human melanoma cells, and human breast carcinoma cells. The IC 50 values obtained with these cells were generally 3–5 times higher than with BAE cells. Inhibition of cell proliferation by apoE was reversible and dependent on the time of apoE addition to the culture. In addition, apoE inhibited the chemotactic response of endothelial cells that were induced to migrate by a gradient of soluble bFGF. Inhibition of cell proliferation by apoE may be mediated both by competition for growth factor binding to proteoglycans and by an antiadhesive activity of apoE. The present results demonstrate that apoE is a potent inhibitor of proliferation of several cell types and suggest that apoE may be effective in modulating angiogenesis, tumor cell growth, and metastasis.