Inhibition by an alkyl-lysophospholipid of the uptake of epidermal growth factor in human breast cancer cell lines in relation to epidermal growth factor internalization.
The effects of 1-O-octadecyl-2-O-methyl-sn-glycerol-3-phosphocholine (ET-18-OCH3), an alkyl-lysophospholipid derivative, on the binding and uptake of labeled epidermal growth factor (EGF) in hormone-dependent (MCF-7 and ZR-75-1) and hormone-independent (BT-20) breast cancer cell lines were investigated at 4 degrees C and 37 degrees C. The total (bound and intracellular) EGF associated with breast cancer cells tested were largely temperature dependent. By pretreatment of the cells with ET-18-OCH3 (10 micrograms/ml) for 12 h, the EGF uptake at 37 degrees C was greatly reduced in both MCF-7 and ZR-75-1 (ET-18-OCH3-susceptible) but not in BT-20 (ET-18-OCH3-resistant) cell lines. The ET-18-OCH3 pretreatment slightly decreased the EGF uptake at 4 degrees C in MCF-7 and ZR-75-1 and had little effect on that in BT-20. The EGF binding at 37 degrees C was unaffected by ET-18-OCH3 in MCF-7 and BT-20 and slightly decreased in ZR-75-1. The EGF binding at 4 degrees C was not changed by ET-18-OCH3 in all cell lines tested. These results suggest that labeled EGF is taken up by the cells in a temperature-dependent manner and ET-18-OCH3 may inhibit this internalization process only in ET-18-OCH3-sensitive human breast cancer cell lines. It is inferrable that the inhibition of the internalization process for EGF may be one of the modes of antitumoral action of ET-18-OCH3.
Kosano
H
H
Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Takatani
O
O
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000493:pharmacokinetics; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D010742:Phospholipid Ethers / Q000494:pharmacology*; D013696:Temperature; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; C055096:1-O-octadecyl-2-O-methylglycerol-3-glucopyranoside; D004815:Epidermal Growth Factor; D005947:Glucose