Glycoprotein 170 induces platelet-activating factor receptor membrane expression and confers tumor cell hypersensitivity to NK-dependent cell lysis.
Multidrug resistance (MDR) confers resistance to anticancer drugs and reduces therapeutic efficiency. It is often characterized by the expression of the MDR1 gene product P-glycoprotein (or gp170) at the membrane of tumor cells. To further propose a potential complementary tool in cancer treatment, the sensitivity of gp170 tumor cells to NK-dependent lysis was investigated. Two kinds of cells were generated from wild-type K562 erythroleukemic cells: the first were derived from Taxol-selected cells and cloned, whereas the second were retrovirally transduced by the cDNA of the MDR1 gene. The last process was also applied to the human embryonal carcinoma cells called Tera-2 cells. First, both cloned and MDR-1 K562 cells appeared highly susceptible to naive NK cell killing. Interestingly, in addition, Tera-2 cells that were not sensitive to NK lysis could be killed when they expressed gp170 at their membranes. In previous data, we demonstrated that NK cell release of bimolecular complexes composed of perforin and platelet-activating factor (PAF) interacting with the PAF-R, which has to be expressed on the target cell membranes, were components of NK tumor cell killing. In the present study, we show that gp170 has the capacity to drive constitutive PAF-R expression on tumor cells, which could be responsible for hypersensitivity to NK lysis and accelerated cell death.
Geromin
Daniela
D
Institut National de la Santé et de la Recherche Médicale, Unité 462, Hôpital Saint Louis, Paris, France.
Bourge
Jean-François
JF
Soulié
Annie
A
Pawliuk
Rob
R
Fleet
Christina
C
Michel
Eugene
E
Denizot
Yves
Y
Berthou
Christian
C
Leboulch
Philippe
P
Sigaux
François
F
Sasportes
Marilyne
M
D018435:ATP Binding Cassette Transporter, Subfamily B; D018236:Carcinoma, Embryonal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000276:immunology*; D019450:Genes, MDR / Q000276:immunology; D006023:Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D012190:Retroviridae / Q000235:genetics; D013724:Teratoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic; D014162:Transfection
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D006023:Glycoproteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D017239:Paclitaxel