Glycoprotein 170 Induces Platelet-Activating Factor Receptor Membrane Expression and Confers Tumor Cell Hypersensitivity to NK-Dependent Cell Lysis

• Published in: The Journal of immunology (1950) 2004-03, Vol.172 (6), p.3604-3611
• Main Authors: Geromin, Daniela, Bourge, Jean-Francois, Soulie, Annie, Pawliuk, Rob, Fleet, Christina, Michel, Eugene, Denizot, Yves, Berthou, Christian, Leboulch, Philippe, Sigaux, Francois, Sasportes, Marilyne
• Format: Article
• Language: English
• Subjects: Carcinoma, Embryonal; Carcinoma, Embryonal - immunology; Carcinoma, Embryonal - metabolism; Carcinoma, Embryonal - pathology; Cell Line, Tumor; Cell Membrane; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Membrane - pathology; Clone Cells; Cytotoxicity, Immunologic; Cytotoxicity, Immunologic - drug effects; Drug Resistance, Neoplasm; Drug Resistance, Neoplasm - immunology; Genes, MDR; Genes, MDR - immunology; glycoprotein gp170; Glycoproteins; Glycoproteins - biosynthesis; Glycoproteins - physiology; Humans; Hydrogen-Ion Concentration; Immunology; K562 Cells; Killer Cells, Natural; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Leukemia, Erythroblastic, Acute; Leukemia, Erythroblastic, Acute - immunology; Leukemia, Erythroblastic, Acute - metabolism; Leukemia, Erythroblastic, Acute - pathology; Life Sciences; MDR1 gene; P-glycoprotein; Paclitaxel; Paclitaxel - pharmacology; Platelet Activating Factor; Platelet Activating Factor - metabolism; Platelet Membrane Glycoproteins; Platelet Membrane Glycoproteins - biosynthesis; platelet-activating factor receptors; Receptors, G-Protein-Coupled; Receptors, G-Protein-Coupled - biosynthesis; Retroviridae; Retroviridae - genetics; Teratoma; Teratoma - immunology; Teratoma - metabolism; Teratoma - pathology; Transduction, Genetic; Transfection
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.6.3604

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.