Tm. Chu et al., DETECTION OF SOLUBLE P-GLYCOPROTEIN IN CULTURE MEDIA AND EXTRACELLULAR FLUIDS, Biochemical and biophysical research communications, 203(1), 1994, pp. 506-512
Multidrug resistance (MDR) is a unique phenomenon in cancer patients a
nd is commonly associated with an overexpression of the human MDR gene
mdr1, which encodes an energy-dependent Mr 180 kDa membrane bound pro
tein, known as P-glycoprotein. P-glycoprotein serves as a membrane eff
lux to pump the drugs out of the cancer cells. Western blot analysis,
using a newly generated monoclonal antibody F4 which recognizes specif
ically an extracellular epitope of human MDR1 P-glycoprotein, reveals
that soluble P-glycoprotein is detected in the cultured media of viabl
e adriamycin-resistant human ovarian carcinoma 2780(AD) cells, whereas
those of the drug-sensitive parent A2780 cells contain no detectable
level of soluble P-glycoprotein. Soluble P-glycoprotein also is detect
ed in extracellular fluids of cancer patients, such as malignant ascit
es and serum, and is not detectable in serum samples of normal healthy
individuals. The Mr of soluble P-glycoprotein is the same as that of
membrane bound P-glycoprotein. The presence of soluble P-glycoprotein
in extracellular fluids may provide the basis for its use as a quantit
ative parameter of MDR and as a means to lessen or reverse MDR. (C) 19
94 Academic Press, Inc.