HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Geromin, D. Articles by Sasportes, M. Search for Related Content PubMed PubMed Citation Articles by Geromin, D. Articles by Sasportes, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB TAXOL

Glycoprotein 170 Induces Platelet-Activating Factor Receptor Membrane Expression and Confers Tumor Cell Hypersensitivity to NK-Dependent Cell Lysis¹

Daniela Geromin^*, Jean-François Bourge^*, Annie Soulié^*, Rob Pawliuk, Christina Fleet, Eugene Michel, Yves Denizot, Christian Berthou^¶, Philippe Leboulch, François Sigaux^* and Marilyne Sasportes^2,*

^* Institut National de la Santé et de la Recherche Médicale, Unité 462, Hôpital Saint Louis, Paris, France; Genetix Pharmaceuticals, Cambridge, MA 02139; Laboratoire de RMN-Physiologie, Université Paris 7, Hôpital Saint Louis, Paris, France; Unité Mixte de Recherche, Centre National de la Recherche Scientifique 6101, Faculté de Médecine, Limoges, France; and ^¶ Service d’Hématologie, Hôpital Morvan, Brest, France

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.