Effect of reduced levels of the LDL receptor of Ehrlich ascites tumor cells on cholesterol uptake and cell proliferation: a coculture study with baby hamster kidney cells.
We have introduced a heterologous coculture model between Ehrlich ascites tumor (EAT) and baby hamster kidney cells (PtK2), and we have studied the influence of PtK2 cells and their newly synthesized cholesterol on uptake and tumor cell proliferation. PtK2 cells produce about five times more cholesterol as compared to EAT cells, and they support tumor cell growth in coculture experiments. This growth stimulation is reduced by 80% when EAT cells are cultured in PtK2 cell-derived medium in the presence of a monoclonal anti-low-density lipoprotein receptor (anti-LDL(r)) antibody. Freshly synthesized cholesterol by PtK2 cells is taken up by EAT cells in a time-dependent manner amounting to a threefold increase after 24 h. Alternatively, cholesterol transfer to EAT cells is decreased between 28% and 35%, when PtK2 cell cholesterol synthesis is inhibited in the presence of mevinolin, the specific inhibitor of the hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Furthermore, lower levels of EAT cell LDL receptor induced by antisense technology reduces cholesterol uptake and cell proliferation. These data demonstrate a metabolic interaction between normal and tumor cells mediated via the exchange of cholesterol, an important membrane constituent.
Haeffner
E W
EW
Abteilung Zelluläre und Molekulare Pathologie, Deutsches Krebsforschungszentrum, INF 280, 69120 Heidelberg, Germany. u.zillmann@dkfz.de
Wittmann
U
U
Kiesewetter
L
L
Zimmermann
H P
HP
Stöhr
M
M
Spiess
E
E
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D018920:Coculture Techniques; D006224:Cricetinae; D007668:Kidney / Q000166:cytology; D008148:Lovastatin / Q000494:pharmacology; D011973:Receptors, LDL / Q000276:immunology / Q000378:metabolism*
D000214:Acyl Coenzyme A; D000911:Antibodies, Monoclonal; D011973:Receptors, LDL; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D002784:Cholesterol; D008148:Lovastatin